Methods and Apparatus for Regulating Blood Pressure

ABSTRACT

A blood pressure control apparatus, system, and methods of modifying intravascular blood flow of a patient is disclosed. In one aspect, the blood pressure control apparatus comprises an intravascular flow-modifying device including an expandable, hollow, stent-like support member configured for implantation within the vasculature, which includes an upstream sensor, a downstream sensor, and a flow restrictor. The flow restrictor is configured to partially occlude a vessel lumen and thereby artificially create back pressure upstream of the device, which causes dilation of the vessel wall and activation of the baroreceptors upstream of the device. Activation of the baroreceptors may depress the activity of the sympathetic nervous system, thereby contributing to a decrease in systemic blood pressure. The flow restrictor is also configured to partially occlude the renal vein lumen, thereby artificially increasing renal perfusion and depressing the baroreceptor-mediated sympathetic and neurohormonal efforts to raise blood pressure.

TECHNICAL FIELD

Embodiments of the present disclosure relate generally to the field ofmedical devices and, more particularly, to an apparatus, systems, andmethods for regulating blood pressure to affect the baroreceptor systemfor the treatment and/or management of various medical disorders.

BACKGROUND

Hypertension and its associated conditions, chronic heart failure (CHF)and chronic renal failure (CRF), constitute a significant and growingglobal health concern. Current therapies for these conditions span thegamut covering non-pharmacological, pharmacological, surgical, andimplanted device-based approaches. Despite the vast array of therapeuticoptions, the control of blood pressure and the efforts to prevent theprogression of heart failure and chronic kidney disease remainunsatisfactory.

Hypertension, or elevated systemic blood pressure, occurs when thebody's smaller blood vessels constrict, causing an increase in systemicblood pressure. Because the blood vessels constrict, the heart must workharder to pump blood through the vasculature and maintain blood flow atthe higher pressures. Sustained periods of systemic hypertension mayeventually result in damage to multiple organ systems, including thebrain, heart, kidneys, peripheral vasculature, and others. Sustainedhypertension may result in heart failure, which is characterized by aninability of the heart to pump enough blood to meet the body'srequirements. Heart failure (and hypertension alone) trigger variousbodily responses to compensate for the heart's inability to pumpsufficient blood to the tissues. Many of these responses are mediated byan increased level of activation of the baroreceptor system, whichoperates without conscious control.

Blood pressure is controlled by a complex interaction of electrical,mechanical, and hormonal forces in the body that are partiallyorchestrated by the baroreflex system, a key mechano-electricalcomponent of blood pressure control, as well as the sympathetic andparasympathetic nervous systems, key electrical components of bloodpressure control. Throughout the body, the blood pressure is modulatedat least in part by the activity of the baroreflex system, a branchingnetwork of stretch receptors extending throughout the vessel walls ofthe cardiovascular system. The baroreflex system connects the brain, theheart, the kidneys, and the peripheral blood vessels, each of whichplays an important role in the regulation of the body's blood pressure.Baroreceptors sense stretch and pressure deformations of the vessel wallin response to changes in blood pressure. For example, an increase inblood pressure causes the arterial walls to stretch, and a decrease inblood pressure causes the arterial wall to return to original size.Baroreceptors send signals reflecting the sensed pressure conditions tothe brain that cause reflexive alterations in the activity of thesympathetic and parasympathetic nervous systems, thereby contributing toadjustments in blood pressure.

The baroreflex system is one of the body's homeostatic mechanisms formaintaining blood pressure. The baroreflex system provides a negativefeedback loop, in which increased blood pressure leads to increasedbaroreceptor activation, which ultimately leads to systemic changesthroughout the body working to decrease the blood pressure. In general,increased baroreceptor activation triggers the brain to decrease thelevel of sympathetic nervous system (SNS) activity and increase thelevel of parasympathetic activity, thereby adjusting the activities ofvarious organs to decrease the blood pressure. With increased SNSactivity, the brain signals the heart to increase cardiac output,signals the kidneys to expand the blood volume by retaining sodium andwater, and signals the arterioles of the peripheral vasculature toconstrict to elevate the blood pressure. Thus, when baroreceptoractivation inhibits SNS activity, the resulting reduction in bloodvolume, reduction in cardiac output, and decrease in peripheralresistance contribute to a decrease in systemic blood pressure.

FIG. 1 shows a schematic illustration of a generic arterial vessel 100including baroreceptors 110 disposed in the vessel wall 120. A networkof baroreceptors extends throughout the walls of the human vasculature,including the arterial and venous vessels. As shown in FIG. 1, thebaroreceptors 100 form arbors 130 or nets extending within the vesselwalls 120. In actuality, because the baroreceptors 100 may be soprofusely distributed and arborized within the vessel walls 120 of themajor vessels, discrete baroreceptor arbors 130 are not readily visible.To this end, those skilled in the art will recognize that thebaroreceptors 110 and baroreceptor arbors 130 depicted in FIG. 1 areprimarily schematic for the purposes of illustration and discussion.

The baroreceptor arbor 130 comprises a plurality of baroreceptors 110,each of which transmits signals to the brain via a nerve 140 in responseto the detected stretch and/or pressure deformations of the vessel wall120. Each baroreceptor 110 is a type of mechanical receptor, such as, byway of non-limiting example, a stretch or pressure receptor, used by thebody to alert the brain to the current blood pressure at individualsites within the vasculature. The baroreceptors 100 sense pressureand/or stretch deformations of the vessel wall 120 in response tochanges in local blood pressure. Typically, an increase in bloodpressure causes the vessel wall 120 to stretch, and a decrease in bloodpressure causes the vessel wall 120 to return to original size. Such achange in arterial wall stretch occurs with every beat of the heart, butthe changes may be more pronounced and/or prolonged in conditions ofsustained hypertension or hypotension. The baroreceptors 110continuously signal the sensed local pressure condition within thevessel 100 to the brain through the nerve 140. Thus, the baroreceptors110 send signals reflecting the sensed local pressure conditions to thebrain, which causes reflexive alterations in the nervous system thatmodulate the systemic blood pressure.

Baroreceptors are profusely distributed in several locations throughoutthe arterial vasculature, including, by way of non-limiting example, theaortic arch, the carotid sinuses, the carotid arteries, the subclavianarteries, the brachiocephalic artery, and the renal arteries.Baroreceptors are also distributed throughout the venous vasculature andthe cardiopulmonary vasculature, including, by way of non-limitingexample, the chambers of the heart, the superior vena cava (SVC), theinferior vena cava (IVC), the jugular veins, the subclavian veins, theiliac veins, the femoral veins, and the renal veins. In addition,baroreceptors and baroreceptor-like receptors may be found in otherperipheral areas such as the intrarenal juxtaglomerular apparatus of thekidney. For the purposes of this disclosure, a baroreceptor is definedas any sensor of pressure and/or stretch deformations in vessel wallssecondary to changes in blood pressure or blood volume within thecardiovascular system. While there may be structural or anatomicaldifferences among the various baroreceptors in the cardiovascularsystem, for the purposes of the present disclosure, activation may bedirected at any of these receptors so long as they provide the desiredeffects of the particular application.

FIG. 2 illustrates the role of the baroreceptors 110 in the maintenanceof cardiovascular homeostasis, including the control of blood pressure145 and cardiac output 145. Changes in local blood pressure are sensedindirectly, through the baroreceptor's sensitivity to mechanicaldeformation during vascular stretch and/or pressurization. The resultantbaroreceptor signals from the individual baroreceptors 110 are processedby the brain 150 to induce activity in a number of body systems tomaintain cardiovascular homeostasis. As illustrated in FIG. 2, thebaroreceptors 110, the body systems, and the requisite nervousconnections therebetween may be collectively referred to as thebaroreflex system 160. Throughout the body, the blood pressure ismodulated at least in part by the activity of the baroreflex system 160,which is formed at least by the brain 150, the heart 165, the kidneys170, the peripheral vessels 180, the nervous system 190, and thebranching network or arbor 130 of baroreceptors 110 extending throughoutthe vessel walls 120 of the cardiovascular system as well as portions ofthe heart 165 and the kidney 170. Baroreceptors 110 send signals thatreflect the sensed local pressure conditions through the nerve 140 andthe nervous system 190 to the brain 150, which is therefore able torecognize changes in blood pressure, one of the indicators of cardiacoutput.

The baroreflex system 160 functions as a negative feedback arc whereinthe level of signaling or activation of the baroreceptors 110 informsthe brain about the current blood pressure conditions and the brainresponds by activating or deactivating either the sympathetic orparasympathetic nervous system to preserve the cardiovascularhomeostasis. Specifically, the baroreflex system 160 provides a negativefeedback loop in which a sensed elevation in blood pressure reflexivelycauses systemic blood pressure to decrease, and a sensed decrease inblood pressure depresses the baroreflex, causing blood pressure to rise.When the blood pressure rises, the vessel wall 120 distends, resultingin stretch and pressure against the baroreceptors 110. Activebaroreceptors fire action potentials or signals more frequently thaninactive baroreceptors. The greater the degree of deformation orstretch, the more rapidly the baroreceptors fire action potentials.

Most baroreceptors are tonically active at mean arterial pressures (MAP)above approximately 70 mm Hg, called the baroreceptor set point. Whenthe MAP falls below the set point, baroreceptors are essentially silent.The baroreceptor set point is not fixed; its value may change withchanges in blood pressure that persist for 1-2 days. For example, inchronic hypertension, the set point may increase; on the other hand,chronic hypotension may result in a depression of the baroreceptor setpoint.

Stimulating the baroreceptors 110 ultimately inhibits the SNS andstimulates the parasympathetic nervous system (PNS), thereby reducingsystemic arterial pressure by decreasing peripheral resistance andcardiac contractility. The sympathetic and parasympathetic branches ofthe autonomic nervous system have opposing effects on blood pressure.Sympathetic activation leads to increased contractility of the heart,increased heart rate, venoconstriction, increased fluid retention, andarterial vasoconstriction, all of which tend to raise blood pressure byelevating the total peripheral resistance, blood volume, and cardiacoutput. Conversely, parasympathetic activation leads to a decrease inheart rate and a minor decrease in contractility, resulting in decreasedcardiac output and therefore a tendency to decrease blood pressure. Bycoupling sympathetic inhibition with parasympathetic activation,increased activation of the baroreceptors 110 may dramatically reduceblood pressure because sympathetic inhibition leads to a drop in totalperipheral resistance and cardiac output, while parasympatheticactivation leads to a decreased heart rate and a reduced cardiac output.Similarly, by coupling sympathetic activation with parasympatheticinhibition, the decreased activation or signaling from the baroreceptors110 may raise blood pressure because sympathetic activation increasesthe total peripheral resistance, increases fluid volume, and elevatescardiac output, and parasympathetic inhibition enhances these effects.

For example, increased local blood pressure causes increased pressure orstretch of the vessel wall 120, causing increased activation orsignaling of the baroreceptors 110, which leads the baroreflex system160 to inhibit SNS activity and stimulate PNS activity to obtain anultimate reduction in systemic blood pressure by a variety ofmechanisms, such as, for example, decreasing peripheral resistancethrough vasodilation of the vessels 180. Conversely, when the localblood pressure is low, a decreased level of activity from thebaroreceptors 110 conveys the low blood pressure to the brain 150, andthe brain 150 interprets the decreased level of baroreceptor activity tomean that the cardiac output is insufficient to meet the body's demands.Consequently, the baroreflex system 160 stimulates reflexive increasesin SNS activity and decreases in PNS activity that alters the behaviorof various organs within the baroreflex system 160, including the heart165, the kidneys 170, the peripheral vessels 180, thereby contributingto an increase in blood pressure to regain cardiovascular homeostasis.Specifically, the baroreflex system 160 activates the SNS and initiatesa neurohormonal sequence in response to a detected drop in local bloodpressure (hypotension) that signals the heart 165 to increase cardiacoutput by increasing the heart rate and increasing the force ofcontraction, signals the kidneys 170 to increase blood volume byretaining sodium and water, and signals the vessels 180 to increaseblood pressure by vasoconstricting (or narrowing).

Unfortunately, the baroreflex system 160 may occasionally contribute tothe exacerbation of a patient's particular cardiovascular condition orhomeostatic imbalance. For example, a patient with chronic hypertensionmay experience local areas of paradoxically decreased blood pressure dueto (1) reduced flexibility in the vessels because of atheroscleroticnarrowing of the blood vessels secondary to the hypertension and (2) areduced cardiac output because of concomitant heart failure secondary tothe hypertension. In such a patient, the baroreflex system 160 maydetect areas of decreased local blood pressure and activate the SNS inresponse to a perceived state of cardiac insufficiency that leads to anexacerbation of hypertension and possible heart failure.

Efforts to control hypertension by combating the consequences ofincreased SNS activity have included drug therapy and surgicalintervention. Drug therapy has included the administration ofmedications such as centrally acting sympatholytic drugs, angiotensinconverting enzyme inhibitors and receptor blockers (intended to blockthe renal renin-angiotensin-aldosterone system), diuretics (intended tocounter the renal sympathetic mediated retention of sodium and water),and beta-blockers (intended to reduce renin release). Although thecurrent pharmacological strategies may alleviate the symptoms of variouscardiovascular and renal disorders related to sympatheticoverstimulation, the strategies have significant limitations, includinglimited efficacy, compliance issues, and side effects. Likewise, thesurgical interventions also possess various limitations. For example,surgical interventions often involve high cost, significant patientmorbidity and mortality, and may not alter the natural course of thedisease.

While the existing treatments may have been generally adequate for theirintended purposes, they have not been entirely satisfactory in allrespects. The intravascular flow-modifying devices, systems, andassociated methods of the present disclosure overcome one or more of theshortcomings of the prior art.

SUMMARY

In one aspect, the present disclosure provides a method of treatinghypertension using an implanted device to regulate blood flow. In oneembodiment, the method includes implanting a flow restricting device inthe vasculature of a patient, sensing blood pressure, and actuating theflow restricting device in response to the sensed blood pressure tomodify the flow of blood through the flow restrictor. In a furtheraspect, the sensor may be used to sense the blood pressure after theactuating step to determine the effect of the modification of the bloodflow. In still a further aspect, the a control system can operate tocontrol the position of the flow restricting device to maintain arelatively constant blood pressure for the patient. In yet a furtheraspect, the flow restricting device includes on-board sensors and apower supply and the method includes controlling the implanted devicewithout inputs from outside the flow constricting construct. In still afurther aspect, the implanted device includes a power harvesting systemand the method includes harvesting power from the human body and usingthe harvested power to actuate the flow restricting device.

In a further embodiment, there is a provided a vascular flow regulationdevice. In one aspect, the flow regulation device comprises an anchoringbody configured for fixed engagement with an vascular wall and a flowconstriction element coupled to the anchoring body, the flowconstriction element being movable between a high flow position and alow flow position. The device further includes an actuator coupled tothe flow constriction element, the actuator configured to move the flowconstriction element between the high flow position and the low flowposition. In one aspect, the actuator may be electrically powered. Inanother aspect, the device may include a power supply carried by theanchoring body.

In still a further embodiment, there is provided a vascular flowregulation device having an on-board sensing system. The flow regulationdevice comprises an anchoring body configured for fixed engagement withan vascular wall and a flow constriction element coupled to theanchoring body, the flow constriction element movable between a highflow position and a low flow position. The flow regulation devicefurther includes a sensing element coupled to the anchoring body andconfigured to detect at least one biometric parameter. In a furtheraspect, the sensing element generates a signal and the flow constrictingdevice moving the flow constricting element between the high flow andlow flow positions in response to the signal. In one aspect, the sensorsenses blood pressure. In still a further aspect, the actuator isconfigured to return to the high flow condition in the absence of power.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory innature and are intended to provide an understanding of the presentdisclosure without limiting the scope of the present disclosure. In thatregard, additional aspects, features, and advantages of the presentdisclosure will be apparent to one skilled in the art from the followingdetailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate embodiments of the devices andmethods disclosed herein and together with the description, serve toexplain the principles of the present disclosure.

FIG. 1 is a cross-sectional schematic illustration of baroreceptorswithin a vessel wall.

FIG. 2 is schematic illustration of baroreceptors within a vessel walland a block diagram illustrating the physiologic connection between thebaroreceptor system, the sympathetic nervous system, and various organsystems.

FIG. 3 is a schematic illustration of the intravascular flow-modifyingdevice positioned in an expanded condition within a vessel lumenaccording to one embodiment of the present disclosure.

FIG. 4 is a schematic illustration of the intravascular flow-modifyingdevice positioned in an expanded condition within a renal vein accordingto one embodiment of the present disclosure.

FIG. 5 is a schematic illustration of a blood pressure regulating systemincluding the intravascular flow-modifying device according to oneembodiment of the present disclosure positioned within the renalanatomy.

FIGS. 6 a and 6 b is a block diagram of the component parts of theintravascular flow-modifying device according to one embodiment of thepresent disclosure.

FIGS. 7 a, 7 b, and 7 d-7 f are schematic illustrations of partiallycross-sectional perspective views of wirelessly communicatingintravascular flow-modifying devices according to different embodimentsof the present disclosure.

FIG. 7 c is a schematic illustration of the intravascular flow-modifyingdevice in an expanded condition according to one embodiment of thepresent disclosure.

FIG. 8 a is a schematic illustration of a perspective view of theintravascular flow-modifying device in a longitudinally expandedcondition according to one embodiment of the present disclosure.

FIG. 8 b is a schematic illustration of a perspective view of theintravascular flow-modifying device illustrated in FIG. 8 a in alongitudinally compressed condition according to one embodiment of thepresent disclosure.

FIG. 9 is a schematic illustration of a perspective view of theintravascular flow-modifying device positioned within a vessel accordingto one embodiment of the present disclosure.

FIG. 10 a is a schematic illustration of a perspective view of theintravascular flow-modifying device in an expanded, activated conditionaccording to one embodiment of the present disclosure.

FIG. 10 b is a schematic illustration of a perspective view of theintravascular flow-modifying device shown in FIG. 10 a in an expanded,partially activated condition according to one embodiment of the presentdisclosure.

FIG. 10 c is a schematic illustration of a perspective view of theintravascular flow-modifying device shown in FIG. 10 a in an expanded,unactivated condition according to one embodiment of the presentdisclosure.

FIG. 10 d is an illustration of a plan view of the disc of theintravascular flow-modifying device shown in FIG. 10 a according to oneembodiment of the present disclosure.

FIG. 11 a is a schematic illustration of a partially cross-sectionalperspective view of a portion of the intravascular flow-modifying deviceshown in FIG. 10 a according to one embodiment of the presentdisclosure.

FIG. 11 b is a schematic illustration of a tab positioned in a recess ina reduced flow position of the intravascular flow-modifying device shownin FIG. 10 a according to one embodiment of the present disclosure.

FIG. 11 c is a schematic illustration of a tab positioned in a recess inan increased or normal flow position of the intravascular flow-modifyingdevice shown in FIG. 10 a according to one embodiment of the presentdisclosure.

FIG. 12 a is a schematic illustration of a perspective view of theintravascular flow-modifying device in an expanded, activated conditionaccording to one embodiment of the present disclosure.

FIG. 12 b is a schematic illustration of a perspective view of theintravascular flow-modifying device shown in FIG. 12 a in an expanded,partially activated condition according to one embodiment of the presentdisclosure.

FIG. 12 c is a schematic illustration of a perspective view of theintravascular flow-modifying device shown in FIG. 12 a in an expanded,unactivated condition according to one embodiment of the presentdisclosure.

FIGS. 13 a-c are schematic illustrations of perspective views of theintravascular flow-modifying device in an expanded, unactivatedcondition according to one embodiment of the present disclosure.

FIG. 13 d is a schematic illustration of a perspective view of theintravascular flow-modifying device shown in FIG. 13 a in an expanded,activated condition according to one embodiment of the presentdisclosure.

FIG. 14 a is a schematic illustration of a perspective view of theintravascular flow-modifying device in an expanded, activated conditionaccording to one embodiment of the present disclosure.

FIG. 14 b is a schematic illustration of a perspective view of theintravascular flow-modifying device shown in FIG. 14 a in an expanded,partially activated condition according to one embodiment of the presentdisclosure.

FIG. 15 a is a schematic illustration of a perspective view of theintravascular flow-modifying device in an expanded, unactivatedcondition according to one embodiment of the present disclosure.

FIG. 15 b is a schematic illustration of a perspective view of theintravascular flow-modifying device shown in FIG. 15 a in an expanded,activated condition according to one embodiment of the presentdisclosure.

FIG. 16 provides a schematic flowchart illustrating methods ofpositioning and controlling blood pressure and the baroreceptor systemusing the blood pressure control system and the intravascularflow-modifying device.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of the disclosure is intended. Any alterations and furthermodifications to the described devices, instruments, methods, and anyfurther application of the principles of the present disclosure arefully contemplated as would normally occur to one skilled in the art towhich the disclosure relates. In particular, it is fully contemplatedthat the features, components, and/or steps described with respect toone embodiment may be combined with the features, components, and/orsteps described with respect to other embodiments of the presentdisclosure. For simplicity, in some instances the same reference numbersare used throughout the drawings to refer to the same or like parts.

The present disclosure relates generally to apparatuses, systems, andmethods using intravascular flow-modifying devices for the treatment ofvarious cardiovascular diseases, including, by way of non-limitingexample, hypertension, chronic heart failure, and/or chronic renalfailure. In some instances, embodiments of the present disclosure areconfigured to manipulate the baroreceptor system, including, by way ofnon-limiting example, the renal baroreceptor system, to increase ordecrease sympathetic activity. In particular, renal baroreceptoractivation of the sympathetic nervous system may worsen symptoms ofhypertension, heart failure, and/or chronic renal failure by causingincreased renal vascular resistance, renin release, and fluid retention,all of which exacerbate hypertension.

Modulation of the renal baroreceptor system using an intravascularflow-modifying device may affect renal sympathetic activity by creatinglocalized increases and drops in blood pressure to activate and/orinactivate the baroreceptors that encircle the renal vessels, includingboth the arteries and the veins, as well as the intrarenalbaroreceptors. By using an intravascular flow-modifying device toselectively manipulate renal baroreceptor activity, a user may affectthe activity of the sympathetic nervous system (SNS) and thereby affectthe activities of various organs, including the brain, heart, kidneys,and peripheral vasculature, to ultimately control the patient's systemicblood pressure.

FIG. 3 illustrates an intravascular flow-modifying device 300, which isconfigured to affect local blood pressure by restricting blood flow andcreating focal areas of increased back pressure, in an expandedcondition and implanted within the generic vessel 100. Theflow-modifying device 300 is shown positioned within the vessel 100adjacent to the vessel wall 120, which contains the arbor 130 ofbaroreceptors 110 connected to the remainder of the baroreceptor system160 through the nerve 140 and the nervous system 190. Blood flowsthrough the vessel 100 from a upstream portion 310 to a downstreamportion 320, as indicated by the dashed arrow. The device 300, includinga support member 325 having an upstream end 340 and a downstream end350, is positioned within a lumen 330 of the vessel 100 immediatelydistal to the baroreceptors 110. In alternative embodiments, theflow-modifying device 300 may be positioned anywhere within the vicinityof baroreceptors and baroreceptor-like receptors. Preferably, the ends340, 350 have sloped or curved circumferential edges 352 to facilitatethe movement of blood through the recess and prevent stagnation of bloodflow within the recess.

The device 300 includes a flow restrictor 360, which is configured toregulate blood flow through the device 300, at least one upstream sensor370, and at least one downstream sensor 372, and a support member 375.The sensors 370, 372 are configured to sense and/or monitor one or moreproperties of blood flow, pressure, or function. As used herein,perfusion, blood perfusion, and renal perfusion generally refer to afluid dynamic property of blood flow such as volumetric flow rate, flowvelocity, and/or pressure, including absolute, mean or pulse pressure,or a fluid static property such as interstitial pressure. The upstreamsensor 370 and the downstream sensor 372 are discussed in more detailbelow with respect to FIGS. 5 and 6 a.

A user may activate or deactivate the intravascular flow-modifyingdevice 300 to affect the local blood pressure in an upstream area 380immediately proximal to the device 300 and thereby modulate theactivation of the baroreceptors 110 located adjacent to the upstreamarea 380. Modulation of the baroreflex system 160 by using theintravascular flow-modifying device 300 to regulate the local bloodpressure in the upstream area 380 has the potential to impactcardiovascular homeostasis by affecting the activities of individualorgan systems within the baroreflex system 160, including, for example,the mechanical and hormonal activities of the heart, the kidneys, andthe vessels. When the flow restrictor 360 is activated in response to auser command, a control system command, and/or sensed data from at leastthe sensors 370 and/or 372, the device 300 functions to partiallyrestrict or occlude blood flow through the device from the proximal end340 to the distal end 350. By at least partially occluding the vessellumen distal (or downstream) of the baroreceptors 110, the back pressureis created proximal (or upstream) of the device 300 such that the vesselwall 120 expands to activate the baroreceptors 110.

For example, a user may create a local increase in blood pressure in theupstream area 380, the vicinity of the baroreceptors 110, by activatingthe flow restrictor 360 to partially occlude blood flow, which createsback pressure at the upstream area 380 to mechanically activate thebaroreceptors 110 by stretching or otherwise deforming them as thevessel wall 120 dilates proximal to the intravascular flow-modifyingdevice 300 to accommodate the back pressure and increased bloodperfusion in the area 380.

In some embodiments, the upstream sensor 370 detects blood perfusioncharacteristics of the vessel 100 at the upstream area 380, and thedownstream sensor detects blood perfusion characteristics of the vessel100 at the downstream area 385. In some embodiments, the flow restrictor360 may be activated or deactivated by the user or a processor inresponse to any of the sensed blood perfusion characteristics of theupstream sensor 370 and/or the downstream sensor 372. In someembodiments, the flow restrictor 360 may be slaved to the upstreamsensor 370 and/or the downstream sensor 372 such that the flow resistoris activated or deactivated in response to any of the sensed bloodperfusion parameters or other sensed characteristics of the upstreamsensor 370 and/or the downstream sensor 372.

In some embodiments, the intravascular flow-modifying device 300includes at least one radiopaque marker 388 to aid in positioning thedevice 300 in the vasculature of the patient. In some embodiments, theradiopaque marker 388 may be spaced along device 300 at a specific andknown distance from the ends 340, 350. The radiopaque marker 388 may aidthe user in visualizing the path and ultimate positioning of the device300 within the vasculature of the patient. In addition, the radiopaquemarker 388 may provide a fixed reference point for co-registration ofvarious imaging modalities and treatments, including by way ofnon-limiting example, external imaging and/or imaging by an internalimaging apparatus (e.g., IVUS). In alternate embodiments, the some orall of component parts of the device 300 are radiopaque to aid inpositioning the device 300 in the vasculature of the patient. Otherembodiments may lack radiopaque markers.

FIG. 4 shows a schematic illustration of the intravascularflow-modifying device 300 positioned within the renal anatomy. The humanrenal anatomy includes kidneys 170 that are supplied with oxygenatedblood by right and left renal arteries 390, each of which branch off anabdominal aorta 400 at the renal ostia 410 to enter a hilum 420 of eachkidney 170. The abdominal aorta 400 connects the renal arteries 390 tothe heart (not shown). Deoxygenated blood flows from the kidneys 170 tothe heart via right and left renal veins 430 and an inferior vena cava440.

Specifically, the intravascular flow-modifying device 300 is shownpositioned in the right renal vein 430 adjacent to the venous wall 450.Baroreceptors 460 include the baroreceptors located within a portion ofthe venous wall 450 located near the right hilum 420 and/or thebaroreceptor-like receptors located within the juxtaglomerularapparatuses of the intrarenal vasculature. Other baroreceptors orbaroreceptor-like receptors may be located in the vessel walls of therenal arteries 390, the abdominal aorta 400, the left renal vein 430,and in the juxtaglomerular apparatuses found in intimate associationwith the intrarenal vasculature (not shown). The device 300 ispositioned within a lumen 470 of the right renal vein 430 at a locationdistal to the baroreceptors 460. In alternative embodiments, theflow-modifying device 300 may be positioned anywhere within the vicinityof baroreceptors, including, but not by way of limitation, the renalarteries 390, the left renal vein 430, the aorta 400, the aortic arch(not shown), the carotid arteries (not shown), and/or the IVC 440,provided the flow regulation produces the desired cardiovascular effect.

In the case of chronic hypertension and/or heart failure, the kidneys170 may interpret decreased blood perfusion in the renal arteries 390,renal veins 430, and other parts of the intrarenal vasculature asreflecting the heart's inability to pump sufficient blood. Renalbaroreceptors 460 respond to this to condition by activating and/orcontributing to a SNS-mediated neurohormonal sequence that signals theheart to increase the heart rate and the force of contraction toincrease the cardiac output, signals the kidneys 170 to expand the bloodvolume by retaining sodium and water, and signals the arterioles toconstrict to elevate the blood pressure. Further, an increase in renalsympathetic activity leads to the increased renal secretion of renin,which activates a cascade of events, including vasoconstriction,elevated heart rate, and fluid retention, through therenin-angiotensin-aldosterone system (RAAS). Vasoconstriction of therenal vasculature causes decreased renal blood flow, which prompts thekidneys 170 to send afferent SNS signals to the brain, triggeringperipheral vasoconstriction and exacerbating hypertension. The kidney170 also produces cytokines and other neurohormones in response toelevated sympathetic activation that can be toxic to other tissues,particularly the blood vessels, heart, and kidney.

Thus, the cardiac, renal, and vascular responses to increased SNSactivity triggered by low renal perfusion cooperate to increase theworkload of the heart, creating a vicious cycle of cardiovascular injurythat accelerates cardiovascular damage and exacerbates heart failure.The present disclosure addresses this kidney-mediated propagation ofhypertension by providing a number of intravascular flow-modifyingdevices by which the kidneys may experience normal or supranormalperfusion even in the face of hypertension (and consequent reducedcardiac output and/or vasoconstriction). By maintaining or augmentingrenal perfusion using a flow-modifying device, the renal baroreceptorsand the baroreceptor-like receptors of the juxtaglomerular apparatusproximal of the flow-modifying device may be modulated to prompt adecrease in blood pressure, and the viscous cycle referred to above maybe stopped or at least moderated to facilitate a return to normal bloodpressure.

By activating the flow restrictor 360 of the intravascularflow-modifying device 300 to partially occlude the outflow of blood fromthe right kidney 170, a user may create an area of artificiallyincreased blood pressure and perfusion in the intrarenal vasculature ofthe kidney 170 and an area 480 of the right renal vein 430 proximal tothe device 300. Renal perfusion and pressure may be artificiallyincreased, thereby increasing the activation of the baroreceptors 460and reducing activation of the SNS to ultimately reduce systemic bloodpressure. In addition, by increasing renal perfusion, the device 300 mayfunction to increase interstitial pressure to reduce sodium and waterabsorption, thereby decreasing blood volume and contributing to adecrease in systemic blood pressure.

FIG. 5 illustrates a blood pressure control system 500 according to oneembodiment of the present disclosure that is configured to selectivelyrestrict intravascular blood flow to regulate local blood pressures inorder to modulate the activity of the baroreflex system and contributeto the maintenance of cardiovascular homeostasis. With respect to theembodiment pictured in FIG. 5, the system 500 comprises theintravascular flow-modifying device 300, a control system 505, whichincludes a controller 510 and peripheral devices 512, at least oneoptional remote sensor 515, and a driver 520.

In FIG. 5, for the purposes of illustration only, the device 300, whichis configured for intravascular placement and/or implantation andincludes the upstream sensor 370 and the downstream sensor 372, is shownpositioned within the right renal vein 430. Therefore, blood will flowfrom the right kidney 170 through the device 300 and into the IVC 440.The sensors 370, 372 are positioned on or in intimate association withthe device 300. In the pictured embodiment, the sensors 370, 372 arepositioned on the device 300 such that the sensor 370 may measurecardiovascular characteristics within an upstream area of the device 300and the sensor 372 may measure cardiovascular characteristics within adownstream area of the device 300.

In alternate embodiments, the device 300 may be positioned at anyintravascular location and/or site within the cardiovascular systemlocated in the vicinity of baroreceptors. Examples of suitable arterialwall locations include, without limitation, a carotid arterial wall, anaortic arterial wall, a subclavian arterial wall, a brachiocephalicarterial wall, a renal arterial wall, a hepatic arterial wall, a splenicarterial wall, a pancreatic arterial wall, a jugular arterial wall, afemoral arterial wall, an iliac arterial wall, a pulmonary arterialwall, a brachial arterial wall, a cardiac arterial wall, a poplitealarterial wall, a tibial arterial wall, a celiac arterial wall, anaxillary arterial wall, a radial arterial wall, an ulnar arterial wall,and a mesenteric arterial wall. Examples of suitable venous walllocations include, without limitation, a hepatic venous wall, aninferior vena cava venous wall, a superior vena cava venous wall, ajugular venous wall, a subclavian venous wall, an iliac venous wall, afemoral venous wall, a pulmonary venous wall, a splenic venous wall, arenal venous wall, a pancreatic venous wall, a cephalic venous wall, atibial venous wall, an axillary venous wall, a brachial venous wall, apopliteal venous wall, a cardiac venous wall, and a brachiocephalicvenous wall.

The exemplary control system 505 generally operates in the followingmanner. The upstream sensor 370, the downstream sensor 372, and/or theremote sensor 515 sense and/or monitor a parameter (e.g., acardiovascular characteristic, component, or flow measurement)indicative of the need to modify the baroreflex system and generate asignal indicative of the parameter. In some instances, the user mayinput command signals into the control system 505. The control system505 generates a control signal as a function of the received sensorand/or command signals. The control signal activates, deactivates, orotherwise modulates the intravascular flow-modifying device 300.Typically, activation of the device 300 results in activation of thebaroreceptors 110 within the adjacent vessel wall 120 (as shown in FIG.3). In the pictured embodiment, activation of the device 300 results inactivation of the baroreceptors 460 within the renal vein wall 450 (asshown in detail in FIG. 4). In alternate embodiments, deactivation ormodulation of the device 300 may cause or modify activation of thebaroreceptors 110.

The intravascular flow-modifying device 300 may comprise a wide varietyof devices which utilize mechanical, electrical, thermal, chemical,biological, hormonal, or other means to activate and/or deactivate thebaroreceptors 110. The device 300, as mentioned above with respect toFIGS. 3 and 4, includes the upstream sensor 370, the downstream sensor372, and the flow restrictor 360. When the sensors 370, 372, and/or 515detect a parameter indicative of the need to modify the baroreflexsystem activity (e.g., excessive blood pressure), the control system 505will typically generate a control signal to activate the device 300,thereby inducing a baroreceptor 110 signal that is perceived by thebrain to be a particular blood pressure state (e.g., hypertension). Whenthe sensors 370, 372, and/or 515 detect a parameter indicative of normalcardiovascular activity (e.g., normal blood pressure), the controlsystem 505 may generate a control signal to partially or completelydeactivate the intravascular flow-modifying device 300.

The sensors 370, 372, and 515 may comprise any suitable sensing devicethat measures, senses, and/or monitors a cardiovascular parameterindicative of the need to modify the activity of the baroreceptor systemby modulating the activity of the device 300. For example, the sensors370, 372, and 515 may comprise a physiologic measurement device thatmeasures blood pressure (systolic, diastolic, average, and/or pulsepressure), blood volumetric flow rate, blood flow velocity, blood pH,gas or element content (such as, by way of non-limiting example, oxygen,carbon dioxide, and/or nitrogen content, mixed venous oxygensaturation), ECG, respiratory rate and/or respiratory efficiency,hemodynamic factors (such as, by way of non-limiting example, hormonesand/or enzymes (e.g., renin, angiotensin, angiotensinogen), bloodglucose, inflammatory mediators, cardiac enzymes, and/or tissuefactors), vasoactivity, nerve activity, and/or tissue activity orcomposition. Exemplary sensors 370, 372, and 515 include, withoutlimitation, ultrasonic sensors, flow sensors, pressure sensors, thermalsensors, blood temperature sensors, electrical contact sensors,conductivity sensors, electromagnetic detectors, chemical or hormonalsensors, pH sensors, and infrared sensors. Specific examples of suitablemeasurement devices for the sensors 370, 372, and 515 include apiezoelectric pressure transducer, an ultrasonic flow velocitytransducer, an ultrasonic volumetric flow rate transducer, athermodilution flow velocity transducer, a capacitive pressuretransducer, a membrane pH electrode, an optical detector, and/or astrain gauge. Examples of additional suitable measurement devices forthe remote sensor 515 include external devices such as, by way ofnon-limiting example, ECG electrodes and a blood pressure cuff. Thesensors 370, 372 are described in more detail below with respect to FIG.6.

Numerous commercially available and experimental sensor devices aresuitable for use in the embodiments of the present disclosure. By way ofillustration only and without limitation to the incorporation ofalternative physiologic sensing devices, a selection of such physiologicsensors can be found in U.S. Pat. Nos. 5,535,752; 5,967,986; 6,152,885;6,113,553; 6,277,078; 6,383,144; 6,430,440 and 6,411,849, each of whichis hereby incorporated by reference in its entirety. In addition toelectrically based sensors to detect blood flow, pressure, temperatureand turbulence, suitable implantable physicologic sensors may includeeither alone or in combination with electrically based sensors set forthabove, chemical sensors or biologic sensors to monitor constituentlevels of metabolites, analytes, electrolytes, and/or proteins in theblood. By way of illustration only and without limitation to theincorporation of alternative physiologic sensing devices, a selection ofsuch chemical and biologic sensors can be found in U.S. Pat. Nos.6,122,536; 5,833,603; 6,673,596; 6,625,479 and 6,201,980, each of whichis hereby incorporated by reference in its entirety.

In addition, the sensors and other components of the embodimentsdescribed herein may include anti-scarring agents to inhibit scarringthat may occur when implanted in the body. U.S. Pub. No. 2010/0092536entitled “Implantable Sensors and Implantable Pumps and Anti-ScarringAgents” discloses a number of suitable compounds and is herebyincorporated by reference in its entirety.

The remote sensor 515 may be positioned separate from the device 300 orcombined therewith. The sensor 515 may be disposed inside the patient'sbody or outside the body, depending on the type of measurement deviceused. For example, the remote sensor 515 may be positioned in or on ablood vessel and/or organ, such as, by way of non-limiting example, achamber of the heart, an artery such as the aortic arch, the abdominalaorta 400, a common carotid artery, a subclavian artery, or thebrachiocephalic artery, or a vein such as the IVC 440, such that atleast one cardiovascular parameter of interest may be readily sensed. Inalternate embodiments, the sensor may be disposed, by way ofnon-limiting example, around an arm of the patient, against the skin ofa patient, or around the finger of a patient. In some embodiments,multiple remote sensors of the same or different types may be positionedat the same or various sites in and/or on the body of the patient toobtain several measurements of one or more cardiovascular parametersfrom various locations within/on the patient's body.

In the pictured embodiment in FIG. 5, the control system 505 includes apower source 508, the controller 510, and the peripheral devices 512.The power source 508 may be a rechargeable battery, such as a lithiumion or lithium polymer battery, although other types of batteries may beemployed. In other embodiments, any other type of power cell isappropriate for power source 508. The power source 508 provides power tothe system 500, and more particularly to the control system 505 and/orthe driver 520. The power source 508 may be an external supply of energyreceived through an electrical outlet. In some examples, sufficientpower is provided through on-board batteries and/or wireless powering.In some embodiments, the power source 508 provides power to the controlsystem 505 as well as the driver 520 and/or the device 300. In otherembodiments, the power source 508 provides power to only the controlsystem 505.

The controller 510 may be in communication with and may perform specificuser-directed control functions targeted to a specific device orcomponent of the system 500, such as the driver 520, the sensors 370,372, and/or 515, the flow restrictor 360, and/or the intravascularflow-modifying device 300. In the pictured embodiment, the peripheraldevices 512 comprise an output device 525 and an input device 527, andthe controller 510 comprises a processor 530 and a memory 535.

The various peripheral devices 512, including the output device 525 andthe input device 527, may enable or improve input/output functionalityof the processor 530. The input device 527 includes, but is notnecessarily limited to, standard input devices such as a mouse,joystick, keyboard, etc. A user may enter information into the inputdevice 527 about the patient, such as age, weight, height, diagnosis,medications, treatments, and so forth. The processor 530 may thendetermine the proper therapeutic thresholds using the user input dataand algorithms stored in the processor 530 and/or the memory 535. Thepatient-specific thresholds may be stored on the memory 535 forcomparison to sensed or measured physiological characteristics.

The output device 525 includes, but is not necessarily limited to,standard output devices such as a printer, speakers, a projector,graphical display screens, etc. The output device 525 may be configuredto display sensed physiological data about the patient,operational/status/mode information about the system 500, and/or alarmindications. For example, the output device 525 may include a display, ahaptic surface, and/or a speaker to provide a visual, a tactile, and/oran audible alarm, respectively, in the event that the patient's sensedphysiological parameters are not within a normal range, as defined basedon the particular patient's medical history and condition as well as ongeneral population guidelines. Such ranges may be calculated or createdto define any of a variety of ranges, including therapeutic range (e.g.,to modulate the baroreceptor system) and/or a safety range (e.g., tomaintain perfusion to tissues downstream of the device 300).

The peripheral devices 525 may also comprise a CD-ROM drive, a flashdrive, a network connection, and electrical connections between theprocessor 530 and various components of the system 500. By way ofnon-limiting example, the processor 530 may manipulate signals from theinput 527 and/or the sensors 370, 372 to generate an graphicalrepresentation of input data (entered and sensed) on a displayscreen-type output device 525, may coordinate subsequentactivation/deactivation of the device 300, and may store the data andthe subsequent treatment plan in the memory 535. The peripheral devices512 may also be used for downloading software containing processorinstructions to enable general operation of the device 300, and fordownloading software implemented programs to perform operations tocontrol, for example, the operation of any auxiliary devices associatedwith and/or attached to the device 300 (e.g., the remote sensor 515).

The processor 530 is typically an integrated circuit with power, input,and output pins capable of performing logic functions. The processor 530may include any one or more of a microprocessor, a controller, a digitalsignal processor (DSP), an application specific integrated circuit(ASIC), a field-programmable gate array (FPGA), or equivalent discreteor integrated logic circuitry. In some examples, processor 530 mayinclude multiple components, such as any combination of one or moremicroprocessors, one or more controllers, one or more DSPs, one or moreASICs, or one or more FPGAs, as well as other discrete or integratedlogic circuitry. The functions attributed to processor 530 herein may beembodied as software, firmware, hardware or any combination thereof.

The processor 530 may include one or more programmable processor unitsrunning programmable code instructions for implementing the thermalneuromodulation methods described herein, among other functions. Theprocessor 530 may be integrated within a computer and/or other types ofprocessor-based devices suitable for a variety of intravascularapplications, including, by way of non-limiting example, baroreceptorstimulation, flow regulation, and intravascular imaging. The processor530 may receive input data from the input device 527, from the device300, and/or from the at least one remote sensor 515 via physicalconnections or wireless mechanisms. The processor 530 may use such inputdata to generate control signals to control or direct the operation ofthe driver 520 and/or the device 300. In some embodiments, the user canprogram or direct the operation of the device 300, the driver 520,and/or the remote sensor 515 from the controller 510 and/or the inputdevice 527. In some embodiments, the processor 530 is in direct wirelesscommunication with the device 300, the driver 520, and/or the remotesensor 515, and can receive data from and send commands to the device300, the driver 520, and/or the remote sensor 515.

In various embodiments, the processor 530 is a targeted devicecontroller that may be connected to the power source 508, the peripheraldevices 512, the memory 335, the driver 520, the remote sensor 515,and/or the intravascular flow-modifying device 300. In such a case, theprocessor 530 is in communication with and performs specific controlfunctions targeted to a specific device or component of the system 500,such as the device 300, without utilizing user input from the inputdevice 527. For example, the processor 530 may direct or program thedevice 300 to function for a period of time in a certain pattern ofactivation/deactivation without specific user input to the controller510. In some embodiments, the processor 530 is programmable so that itcan function to simultaneously control and communicate with more thanone component of the system 500, including the peripheral devices 512,the power source 508, the driver 520, the memory 535, and/or the device300. In other embodiments, the system includes more than one processorand each processor is a special purpose controller configured to controlindividual components of the system. In some embodiments, the processormay include a plurality of processing units employed in a wide range ofcentralized or remotely distributed data processing schemes.

The memory 535 is typically a semiconductor memory such as, by way ofnon-limiting example, read-only memory, a random access memory, and/orother computer storage media. The memory 535 interfaces with processor530 such that the processor 530 can write to and read from the memory535. For example, the processor 530 can be configured to read data fromthe device 300 and/or the remote sensor 515 and write that data to thememory 535. In this manner, a series of data readings can be stored inthe memory 535. The memory 535 may contain data related to the sensorsignals from sensors 370, 372, and/or 515, the command signals generatedby the processor 530, and/or the values and commands provided by theinput device 527. The processor 530 may be capable of performing basicmemory management functions, such as erasing or overwriting the memory535, detecting when the memory 535 is full, and other common functionsassociated with managing semiconductor memory.

Any computer-readable media may be used in the system as the memory 535for data storage. Computer-readable media are capable of storinginformation that can be interpreted by the processor 530. Thisinformation may be data or may take the form of computer-executableinstructions, such as software applications, that cause the processor530 to perform certain functions and/or computer-implemented methods.Depending on the embodiment, such computer-readable media may comprisecomputer storage media and communication media. Computer storage mediaincludes volatile and non-volatile, removable and non-removable mediaimplemented in any method or technology for storage of information suchas computer-readable instructions, data structures, program modules, orother data. Computer storage media includes, but is not limited to, RAM,ROM, EPROM, EEPROM, flash memory or other solid state memory technology,CD-ROM, DVD, or other optical storage, magnetic cassettes, magnetictape, magnetic disk storage or other magnetic storage devices, or anyother medium which can be used to store the desired information andwhich can be accessed by components of the system 500.

The processor 530 and/or the memory 535 may also include softwarecontaining one or more algorithms defining one or more functions orrelationships between the command signals and the sensor signals. Thealgorithm may dictate activation or deactivation commandprotocols/signals depending on the received sensor signals ormathematical derivatives thereof. The algorithm may dictate anactivation or deactivation control signal when a particular sensorsignal falls below a predetermined threshold value, rises above apredetermined threshold value, or when the sensor signal indicates aspecific physiologic event or condition.

As mentioned above, the intravascular flow-modifying device 300 may beconfigured to activate baroreceptors mechanically, electrically,thermally, chemically, biologically, or otherwise. In some embodiments,the blood pressure control system 500 includes the driver 520 to providethe appropriate power mode for the device 300. For example, if thedevice 300 utilizes pneumatic or hydraulic actuation, the driver 520 maycomprise a pressure/vacuum source and the driver cable 555 may comprisea fluid/gas line(s). In the alternative, if the device 300 utilizeselectrical or thermal actuation, the driver 520 may comprise a poweramplifier or the like and the driver cable 555 may comprise anelectrical lead(s). In the alternative, if the device 300 utilizeschemical or biological actuation, the driver 520 may comprise afluid/chemical reservoir and a pressure/vacuum source, and the drivercable 555 may comprise a fluid/gas line(s). In the alternative, if thedevice 300 utilizes imaging or ultrasonic actuation, the driver 520 maycomprise an ultrasound energy generator.

Under the user-directed or automated (algorithm-based) operation of thecontroller 510, the driver 520 may generate a selected form andmagnitude of energy (e.g., a particular energy frequency) best suited toa particular application. The user may use the input device 527 and thecontroller 510 to initiate, terminate, and adjust various operationalcharacteristics of the driver 520. Under the control of the user or anautomated control algorithm in the processor 530, the driver 520generates a desired form and magnitude of energy. The driver 520 may beutilized with any of the intravascular flow-modifying devices describedherein for delivery of energy with the desired field parameters, i.e.,parameters sufficient to induce activation and/or deactivation of thedevice to modify intravascular flow and thereby modulate thebaroreceptor system. It should be understood that the intravascularflow-modifying devices described herein may be connected, electricallyor otherwise, to the driver 520 even through the driver 520 is notexplicitly shown or described with respect to each embodiment.

In the pictured embodiment, the driver 520 is located external to thepatient. In other embodiments, the driver 520 may be positioned internalto the patient. In some embodiments utilizing an intravascularflow-modifying device, for example, the driver 520 may be a componentpart of the device 300 itself, as discussed below with respect to FIG.6. In other embodiments, the driver 520 may not be necessary,particularly if the processor 530 and/or the device 300 itself generatesa sufficiently strong electrical signal for low level electrical orthermal actuation of the device 300. In some embodiments, for example,the driver may additionally comprise or may be substituted with analternative energy generator, such as, by way of non-limiting example, athermoelectric polymer or a dielectric elastomer structure configured toproduce energy. The control and direction of the energy supplied by thedriver 520 will be described in further detail below with respect toFIG. 6 a.

In various embodiments, the controller 505 may be operatively coupled tothe flow-modifying device 300 by way of electric control cables orleads, wireless communication mechanisms, or a combination thereof. Inaddition, the controller 505 may be implanted in whole or in part withinthe body of the patient. In some embodiments, the entire controller 505may be carried externally with the patient either (1) utilizing wirelesscommunication between the device 300 and the controller 505, or (2)utilizing transdermal connections between the device 300 and thecontroller 505. For example, the controller 505 and/or the driver 520may comprise an external control device or handheld programming deviceto operate and/or power the intravascular device 300. Alternatively, thecontroller 505 and the driver 520 may be implanted in the body of thepatient (e.g., subcutaneous implantation) while the peripheral devices512, which may be coupled to the controller 505 via transdermalconnections, may be carried externally. As a further alternative, thetransdermal connections may be replaced by wireless communicationmethods, such as, by way of nonlimiting example, cooperatingtransmitters and receivers positioned on various components of thesystem 500 to allow remote communication between various components ofthe system 500. Such wireless communication methods will be described inmore detail below in relation to FIGS. 6 a and 6 b.

In some embodiments, the system 500 may be configured to include aplurality of electrical connections, each electrically coupled to adifferent component (e.g., an electrode, a sensor, and/or a flowrestrictor) on the device 300 via a dedicated conductor and/or a sensorcable, running transdermally and/or intravascularly between the device300 to the control system 505 and/or the driver 520. Such aconfiguration may allow for a specific group or subset of components onthe device 300 to be easily energized or powered by the driver 520. Sucha configuration may also allow the device 300 to transmit data from anyof a variety of sensors to the control system 505. In alternativeembodiments utilizing wireless modes of communication between thecontrol system 505, the driver 520, and/or the device 300, the wirelesscommunication mechanisms may allow for similarly specific and directcommunication between the individual components of the system 500.

For example, in the pictured embodiment, the processor 530 isoperatively coupled to the sensors 370, 372 (and/or a communicationmodule, as described below in relation to FIG. 6 a) on the intravascularflow-modifying device 300 by way of a sensor cable or lead 540. Inalternate embodiments, the processor 530 may be wirelessly coupled tothe sensor 370 and/or the sensor 372 (and/or a communication module) onthe intravascular flow-modifying device 300. Similarly, the processor530 is shown operatively coupled to the at least one remote sensor 515by way of a sensor cable or lead 545. In alternate embodiments, theprocessor 530 may be wirelessly coupled to the at least one remotesensor 515. Thus, in various embodiments, the controller 505 receives asensor signal from the sensors 370, 372, and/or 515 and/or acommunication module (and/or a communication module) either wirelesslyor by way of sensor cables 540 and/or 545, and transmits control signalsto the device 300 either wirelessly or by way of a command cable 550linking the processor 530 to the driver 520 and/or a driver cable 555linking the driver 520 to the device 300.

The blood pressure control system 500 may operate as a closed looputilizing feedback from the sensors 370, 372, and/or 515, or as an openloop utilizing commands received from the user through the input device527. The patient and/or treating physician may provide commands to theinput device 527. The output device 525 may be used to display thesensor data/signal, the command signal, and/or the software and storeddata contained in the memory 535. Thus, during the open loop operationof the system 500, the user may utilize some feedback from the sensors370, 372, and/or 515, which may be displayed to the user on the outputdevice 525, but the user may also operate the system 500 without anysensor feedback. Commands received by the input device 527 may directlyinfluence the command signals issued by the processor 530 or may alterthe software and related algorithms contained in the processor 530and/or the memory 535.

In a closed loop, if the sensor 515 detects a reduction in cardiacoutput or systemic blood pressure, or if the sensor 370 detects areduction in renovascular pressure, the control system 505 may generatean activation command signal to activate the device 300, therebyincreasing renovascular perfusion such that the kidney 170 does notexperience reduced blood flow (renal perfusion). When the sensor 515 orthe sensor 370 detects the desired improvement or normalization of thesensed parameter (e.g., blood pressure), the control system 505 maygenerate a control command to deactivate or modify the flow restrictionactivity of the device 300.

In some embodiments, command signals generated by the processor 530 inresponse to user input from the input device 527 may override thecommand signals generated by the processor 530 in response to senseddata from the sensors 370, 372, and/or 515.

The processor 530 may contain information about the sensors 370, 372,and/or 515, such as what type of sensor it is (e.g., what the sensordetects, and how) and the location of the sensor (e.g., whether thesensor is located within the device 300, intravascularly, or outside thepatient's body). Such information may be used by the processor 530 toselect appropriate algorithms, lookup tables, and/or calibrationcoefficients stored in the processor 530 and/or the memory 535 forcalculating the patient's appropriate physiological parameters. Inaddition, the processor 530 may contain information specific to thepatient, such as, for example, the patient's age, weight, cardiovascularhistory, and diagnosis. This information may allow the processor 530 todetermine patient-specific threshold ranges in which the patient'sphysiological parameter measurements should fall and to enable ordisable additional physiological parameter algorithms, such as alarmthreshold ranges for the output device 525 of the system 500. Moreover,the memory 535 may store such information for communication to theprocessor 530. By way of non-limiting example, the memory 535 may storethe type and location of various sensors, the mechanism of action ofvarious sensors, the proper algorithms to be used for calculating thepatient's physiological parameters and/or alarm threshold values, thepatient characteristics to be used for calculating the alarm thresholdvalues, and the patient-specific threshold values to be used formonitoring the physiological parameters.

The processor 530 may be configured to calculate physiologicalparameters based on data inputted from the user through the input device327 and the data received from the sensors 370, 372, and/or 515 relatingto cardiovascular conditions. The processor may relay such informationand calculations to the output device 525 for display to the user. Asmentioned above, the output device may generate a visual, audible, ortactile warning to alert the user to sensed cardiovascular parametersthat may require medical attention, including adjustment (e.g.,activation or deactivation) of the device 300. In addition, theprocessor 530 may be connected to a network to enable the sharing ofinformation with servers or other workstations (not shown).

The command signal generated by the processor 530 may be continuous,periodic, episodic, or a combination thereof, as dictated by analgorithm contained in the processor 530 and/or the memory 535.Continuous command signals include a constant pulse, a constant train ofpulses, a triggered pulse, and a triggered train of pulses. Examples ofperiodic command signals include each of the continuous control signalsdescribed above which have a designated start time (e.g., the beginningof each minute, hour, or day) and a designated duration (e.g., 1 second,1 minute, or 1 hour). Examples of episodic command signals include eachof the continuous command signals described above which are triggered bya specific event, condition, or episode (e.g., activation by the user,an increase in sensed blood pressure above a certain threshold, etc.).

The processor 530 may be programmed to operate the device 300 in a rangeof power consumption modes, wherein the processor 530 issues continuous,periodic, episodic, and/or a combination thereof of command signals tothe device 300, thereby controlling the amount of power to the device300 and the activity of individual device components, such as, but notlimited to, the sensors 370, 372, and/or 515 and the flow restrictor360. In terms of operating in different power consumption modes, thesensors 370, 372 may be configured to operate in multiple modes thateach consume a different amount of power. In all the embodimentsdescribed herein, each individual power consumption mode may correspondto using a different mix of sensors and/or a different data samplingregime. For example, in a high power consumption mode, one of or boththe sensors 370, 372 may receive periodic command signals from theprocessor 530 to sense a particular characteristic only at certaininterval for a limited duration. Depending on the current powerconsumption mode that the device 300 is operating in, one or more of thesensors may be de-energized to save power.

For example, in a high power consumption mode, the processor 530 mayissue a continuous command signal to the sensors to sense variousintravascular characteristics continuously. In a low power consumptionmode, in contrast, the processor 530 may be programmed to issueperiodic, episodic, and/or a combination of periodic and episodiccommand signals to the device 300, thereby minimizing the amount ofactivity of the sensors 370, 372 and/or the flow restrictor 360. In oneexample, the processor 530 may issue a periodic command signal regimedirecting the sensors to only sense a particular intravascularcharacteristic for 5 seconds every 60 seconds. In a low powerconsumption mode, the processor 530 may also selectively activateparticular sensors without activating others. For example, if theupstream sensor 370 reports data confirming a stable cardiovascularstate, the processor 530 may not direct the downstream sensor to detectanything.

The particular voltage, current, and frequency delivered to the device300 may be varied in different power consumption modes as needed. Forexample, electrical energy can be delivered to the device 300 at aparticular voltage, at a particular current, at a particular frequency,at a particular pulse-width, and at a particular combination of theforegoing to modulate the energy delivery to the device 300 dependingupon the particular power consumption mode of the device 300 at anygiven time. Moreover, electrical energy can be delivered in a unipolar,bipolar, and/or multipolar sequence or, alternatively, via a sequentialwave, charge-balanced biphasic square wave, sine wave, or anycombination thereof depending upon the particular power consumption modeof the device 300 at any given time.

The processor 530 may select the mode of operation for the device 300 inreal-time based on an analysis of the data obtained from the sensors370, 372, and/or 515, or in response to input commands inputted into theinput device 527 by a user. It should be understood that the variouspower consumption modes may comprise any of a variety of command signalregimes, provided certain modes permit the device 300 to consume lesspower and other modes direct the device 300 to consume more power.

The memory 535 may also store information for use in selection of apower consumption mode based on the data generated by sensors 370, 372,and/or 515 and/or the user inputs into the input device 327. Forexample, in some embodiments utilizing episodic command signal regimes,the memory 535 stores one or more data profiles that may be used todetermine when the sensed data indicates that the device 300 shouldswitch to a low power mode. A data profile may be an algorithm, table,or other representation of standard data to which the patient-specificdata may be compared. If a match is detected between thepatient-specific data and the relevant data profile, then the system 500may switch to a low power mode of operation until some sensed trigger orepisode causes the system to switch to another power consumption mode(e.g., to a high power consumption mode). Furthermore, the data profilesmay identify which power consumption mode to use when a particular dataprofile is matched by the sensed data.

In some embodiments, the various power consumption modes may also bestored in the memory 535. For example, the memory 535 may include alisting of specific actions to be performed or not to be performed, or alist of components to be energized or de-energized while in a specificpower mode. For example, if the sensors detect and report data conveyinga normotensive cardiovascular state, and the normotensive data matches anormotensive data profile store on the memory 535, the system 500 mayswitch to a low power mode of operation during which neither the flowrestrictor 360 nor the sensors 370, 372 are energized, or during whichthe sensors are energized on a periodic basis. Alternatively, in ahardware embodiment the various power modes may be incorporated into thehardware or firmware of the system.

FIG. 6 a schematically shows the component parts of the intravascularflow-modifying device 300 in an expanded condition according to oneembodiment of the present disclosure. The intravascular flow-modifyingdevice 300 comprises an expandable support body 600 configured forinsertion into a blood vessel and for stable implantation within theblood vessel. The support body 600 is shaped as a hollow, generallycylindrical tube that extends from the proximal end 340 to the distalend 350 of the device 300 and includes a main body portion 602 extendingtherebetween. The main body portion 602 houses the flow restrictor 360,the upstream sensor 370, and the downstream sensor 372. In addition, themain body portion 602 houses a driver 605 that is coupled to the flowrestrictor and/or a microprocessor 610, a power supply 615 that maypower various components of the device 300, and a communication module620 that enables bidirectional communication between the device 300 andthe control system 505 (and/or the remote sensor 515 shown in FIG. 5).Some embodiments may include at least one auxiliary sensor 625, whichmay be substantially similar in form and function to any of the sensors370, 372, or 515. These individual components of the device 300 may beembedded within or disposed upon the expandable support body 600. Inembodiments having individual components disposed upon the support body600, individual components may be coupled to the support body 600 by anyof a variety of attachment mechanisms, including, but not limited to,biologically compatible adhesive, welding, chemical bonding, andmechanical fasteners.

The support body 600 is configured to be an elongate, relativelyflexible, cylindrical tube having an unexpanded condition and anexpanded condition. Typically, the support body 600 has a structure thatminimizes the risk of damage to individual components of the device 300when the support body 600 is transformed between an unexpanded conditionand an expanded condition. The flexible and expandable properties of theexpandable support body 600 facilitates percutaneous delivery of theexpandable support member, while also allowing the expandable supportbody 600 to conform to an intraluminal portion of a blood vessel (asillustrated in FIG. 3). In the expanded condition, the support body 600has a generally circular cross-sectional shape for conforming to thegenerally circular cross-sectional shape of a blood vessel lumen. Byconforming to the shape of a blood vessel lumen, the expandedconfiguration of the support body 600 facilitates movement of the bloodflow therethrough while also maintaining lumen patency. In someembodiments, the support body 600 may be sized and configured forexpansion, manipulation, and use within a renal vessel.

The structure of the expandable support body 600 may be, by way ofnon-limiting example, a mesh, a zigzag wire, a spiral wire, anexpandable stent, or other similar configuration that defines a lumen630 and allows the support body 600 to be collapsed and expandedintravascularly. The support body 600 may be fabricated from aself-expanding material biased such that the exterior surface of thesupport body 600 expands into contact with the vessel luminal wall uponexpanding the device 300. Thus, the support body 600 may be comprised ofa material having a high modulus of elasticity, including, for example,cobalt-nickel alloys (e.g., Elgiloy), titanium, nickel-titanium alloys(e.g., Nitinol), cobalt-chromium alloys (e.g., Stellite),nickel-cobalt-chromium-molybdenum alloys (e.g., MP35N), graphite,ceramic, stainless steel, and hardened plastics. The expandable supportbody 600 may also be made of a radiopaque material or include radiopaquemarkers (e.g., radiopaque markers 388, as shown in FIG. 3) to facilitatethe fluoroscopic visualization of the intravascular positioning andplacement of the device 300.

The support body 600 may include at least one therapeutic agent foreluting into the vascular tissue and/or blood stream. The therapeuticagent may be capable of counteracting a variety of systemic and localpathological conditions including, but not limited to, hypertension,hypotension, thrombosis, stenosis, and inflammation. Accordingly, thetherapeutic agent may include at least one of an anti-hypertensive, ananti-hypotensive agent, an anticoagulant, an antioxidant, afibrinolytic, a steroid, an antiapoptotic agent, and/or ananti-inflammatory agent. In some embodiments, the therapeutic agent maybe capable of treating or preventing other diseases or disease processessuch as microbial infections and heart failure. In these instances, thetherapeutic agent may include an inotropic agent, a chronotropic agent,an anti-microbial agent, and/or a biological agent such as a cell,peptide, or nucleic acid. The therapeutic agent may be linked to theinterior or exterior surface of the support body 600, embedded andreleased from within polymer materials, such as, by way of non-limitingexample, a polymer matrix, or surrounded by and released through acarrier member (not shown) that is associated with the support body 600.

In some embodiments, the expandable support body 600 includes aninsulative material 635 for isolating blood flow through the vessel 12from any electric current flowing through the device 300. Thus, theinsulative material 635 may serve as an electrical insulator, separatingelectrical energy from the surrounding blood flow and tissue andfacilitating efficient delivery of the electrical energy to individualcomponents of the device 300. The insulative material 635 generally hasa low electrical conductivity and a non-thrombogenic surface. Theinsulative material 635 may include materials such as, by way ofnon-limiting example, PTFE, ePTFE, silicone, silicone-based materials,elastomeric materials, an ultraviolet cure or heat shrink sleeve,polyethelene, Nylon™, and the like. In the pictured embodiment, theinsulative material 635 is disposed around the support body 600 andextends along the entire exterior and interior length of the body 600.Alternatively, the insulative material 635 may be attached to selectportions of the device 300, including, but not limited to, theexpandable support body 600, the sensors 370, 372, and the power supply615. Additionally or alternatively, the insulative material 635 may bedisposed about the luminal surface of the expandable support body 600,the non-luminal surface of the support body 600, or may be wrappedaround both the luminal and non-luminal surfaces. The insulativematerial may be attached around the entire circumference of theexpandable support body 600 or, alternatively, may be attached in piecesor interrupted sections to allow the expandable support body 600 to moreeasily expand and contract.

In some embodiments, at least a portion of the device 300, including thesupport body 600 and/or other individual components of the device 300,may optionally include a layer (not shown) of biocompatible material.The layer of biocompatible material may be synthetic such as Dacron®(Invista, Wichita, Kans.), Gore-Tex® (W. L. Gore & Associates,Flagstaff, Ariz.), woven velour, polyurethane, or heparin-coated fabric.Alternatively, the layer of biocompatible material may be a biologicalmaterial such as, by way of non-limiting example, bovine or equinepericardium, peritoneal tissue, an allograft, a homograft, patientgraft, or a cell-seeded tissue. The biocompatible layer may cover eitherthe luminal surface of the expandable support body 600, the non-luminalsurface of the support body 600, or may be wrapped around both theluminal and non-luminal surfaces. The biocompatible layer may beattached around the entire circumference of the expandable support body600 or, alternatively, may be attached in pieces or interrupted sectionsto allow the expandable support body 600 to more easily expand andcontract.

The flow restrictor 360 is disposed within the expandable support body600 such that the flow constrictor 360, when activated, may partiallyocclude the vessel lumen. The flow restrictor 360 may be configured toinclude any of a variety of forms and mechanisms of action, providedthat the flow restrictor can partially occlude blood flow through thedevice 300 and thereby create an area of artificially increased bloodpressure immediately upstream of the device 300 which modulates theactivity of baroreceptors in the vicinity.

The driver 605 comprises an actuator apparatus coupled to the flowrestrictor 360 such that the driver 605 may impel the flow restrictor360 to change from an inactivated condition to an activated conditioncapable of restricting flow through the lumen 630 of the support body600. For example, upon receiving an activation signal from themicroprocessor 610, the driver 605 actuates or activates the flowrestrictor 360, moving it from an inactive position or a less activeposition to a more active position, thereby increasing the degree ofocclusion within the support body 600 and the vessel lumen. Conversely,upon receiving a deactivation signal from the microprocessor 610, thedriver 605 deactivates the flow restrictor 360, moving it from a moreactive position to a less active position, thereby decreasing the degreeof occlusion within the support body 600 and the vessel lumen. Variousspecific embodiments of a driver may be described below in relation toFIGS. 7-15 b. By way of non-limiting example, the driver may comprise orbe coupled to any of an actuating rod, a helical coil, a motor, apiston, and/or a pump.

As mentioned above in relation to FIGS. 3 and 5, exemplary sensors 370,372 may include, without limitation, ultrasonic sensors, flow sensors,thermal sensors, such as thermocouples, thermistors and infraredsensors, pressure sensors, electrical contact sensors, conductivityand/or impedance sensors, electromagnetic detectors, fluid flow sensors,electrical current sensors, tension sensors, chemical or hormonalsensors (capable of detecting the concentration or presence/absence ofvarious gases, ions, enzymes, proteins, metabolic products, etc.), andpH sensors. The expandable support body 600 may contain any of a varietyof sensor types within a single embodiment. As a result, the device 300may be capable of simultaneously examining a number of differentcharacteristics of the blood and surrounding tissue, the surroundingenvironment, and/or the device itself within the body of a patient,including, by way of non-limiting example, vessel wall temperature,blood temperature, device temperature, fluorescence, luminescence, flowrate, and flow pressure.

The sensors 370, 372 may comprise raised components or flat componentson the surface of the support body 600. The sensors 370, 372 may belocated at any position along the length of the body 600, provided thatthe sensor 370 is positioned upstream to the flow restrictor 360, andthe sensor 372 is positioned downstream to the flow restrictor 360. Thesensors may be coupled to the expandable support body using any of avariety of known connection methods, including by way of non-limitingexample, welding, biologically-compatible adhesive, and/or mechanicalfasteners. For example, in one embodiment, the sensors 370, 372 may beadhesively bonded to the body 600 using Loctite 3311 or any otherbiologically compatible adhesive. In some embodiments, the sensors maybe integrally formed with the support body 600. For example, in someembodiments, at least one sensor 370, 372 may be comprised of flexiblecircuits integrated into the support body 600. The flexible circuit maybe comprised of polymer thick film flex circuit that incorporates aspecially formulated conductive or resistive ink that is screen printedonto the flexible substrate to create the sensor circuit patterns. Thissubstrate is then adhered to a surface of the support body 600 orintegrated with the support body 600.

In addition to the upstream sensor 370 and the downstream sensor 372,the device 300 may include any number of ancillary sensors 625positioned on the exterior, vessel wall-contacting surface of thesupport body 600. Except for their position, the ancillary sensors maybe configured to be substantially similar to sensors 370, 372. Exemplaryancillary sensors 625 include, without limitation, ultrasonic sensors,flow sensors, thermal sensors, blood temperature sensors, electricalcontact sensors, conductivity sensors, electromagnetic detectors,chemical or hormonal sensors, pH sensors, and infrared sensors. Forexample, in one embodiment the ancillary sensor 625 may comprise athermal sensor positioned on the exterior vessel wall-contacting surfaceof the support body 600, thereby permitting the sensor 625 to measure acharacteristic of the vessel wall (e.g., temperature) whilesimultaneously the sensors 370, 372 may measure a cardiovascularcharacteristic within the vessel lumen.

In some embodiments, each sensor 370, 372, and/or 625 includes sensorcables (not shown) coupling the sensor to at least the microprocessor610 and/or the communication module 620. In alternate embodiments,several sensors may be coupled to the microprocessor 610 and/or thecommunication module 620 using one or more shared sensor cables. Inalternate embodiments, the sensors may communicate with themicroprocessor 610 and/or the communication module 620 via any of avariety of wireless means.

The communication module 620 is configured to relay information, such ascommand signals from the processor 530 and sensed data from the sensors370, 372, between the device 300 and the control system 505. Thecommunication module 620 may contain transmitter circuitry and receivercircuitry that together carry out the bidirectional communication withthe control system 505. The communication module 620 may cooperate withthe control system 505 to actively control power transmission,activation energy, power mode, and/or an activation protocol. In someembodiments, the communication module may operate in a closed loopfashion by actively controlling power transmission, activation energy,power mode, and/or an activation protocol for the device 300 withoutreceiving instructions from the control system 505. Instead, thecommunication module 620 may communicate internally with the sensors370, 372, the power supply 615, the microprocessor 610, and/or thedriver 605 to operate the device 300. In some embodiments, thecommunication module 620 may operate in both an open loop and closedloop fashion to operate the device 300.

In some embodiments, the communication module is coupled to the controlsystem 505 via sensor cables 540, as described above in relation to FIG.5. In other embodiments, the communication module 620 is coupled to thecontrol system 505 via wireless means. In such embodiments, asillustrated in FIG. 6 b, the communication module 620 may include anantenna 640 and a transceiver 645 coupled to the antenna 640. Theantenna 640 is capable of sending signals to the control system 505 andreceiving signals from the control system 505. In some embodiments, thesignals are transmitted and received at Radio Frequencies (RF).

The device 300 includes a microprocessor 610 that is coupled to thecommunication module 620. Specifically, the microprocessor may becoupled to the transceiver 645. Based on the output of the transceiver645 (i.e., the input received from the control system 505), themicroprocessor runs firmware 650, which is a control program, to operatecontrol logic 655, which is the dedicated software code that is writtento operate the device 300. In embodiments configured for wirelesscommunication, the control logic 655 may include digital circuitry thatis implemented using a plurality of transistors, for example FieldEffect Transistors (FETs). In the pictured embodiment, the firmware 650and the control logic 655 are integrated into the microprocessor 610. Inalternate embodiments, the firmware 650 and/or the control logic 655 maybe implemented separately from the microprocessor 610. As mentionedabove, the driver 605 controls the flow restrictor 630 upon receiving anoutput signal from the microprocessor 610.

The power supply 615 is configured to provide power to the othercomponents of the device 300, and may include power circuitry 660 and arechargeable power source 665. In some embodiments, the power source 665includes a battery that may be coupled to an external power supply via acable (not shown). In other embodiments, the power source 665 includes areceiving coil that is part of a transformer (not shown). In that case,the transformer also includes a remote charging coil that is positionedexternal to the power source 665 and inductively coupled to a receivingcoil of the power source 665. Thus, as described in more detail belowwith reference to FIGS. 7 b-7 f, the power source 665 may obtain energyfrom the inductive coupling between a receiving coil of the power source665 and the remote charging coil. In alternate embodiments, the powersource 665 includes both a battery and a receiving coil.

In alternate embodiments, the power source 665 utilizes a piezoelectricmechanism, such as, by way of non-limiting example, a piezoelectriccrystal and a piezoelectric wire, to generate RF energy. In alternateembodiments, the power source 665 includes both a battery and apiezoelectric crystal. In some embodiments, the power source 665utilizes an amplifier (not shown) to amplify the RF signal generatedwirelessly through either an inductive coupling or a piezoelectricmechanism. In some embodiments, the power source 665 utilizes an AC/DCconverter to supply power the individual components of the device 300.

In any case, the power source 665 must provide a sufficient amount ofpower to meet the needs of the device 300 and must be small enough tofit within the slim profile of the support body 600 that is preferredclinically. The power source 665 may, but need not be, rechargeable.Whether or not the power source is rechargeable, given the relativelysignificant power requirements of the various on-board sensors 370, 372,and the relatively limited amount of power available in a power sourcesmall enough to be integrated into the device 300, prudent powermanagement must be employed to enable the device 300 to operate withoutnecessitating that the device 300 be removed from the vasculature forreplacement, and/or, if applicable, recharging of the power source.

This challenge may be overcome by a combined power conservation approachthat involves power consumption mode protocols orchestrated by the user,the control system 505 (as described above in relation to FIG. 5),and/or the device 300 itself. The microprocessor 610, the sensors 370,372, and the power supply 615 may cooperate to direct the device 300through a variety of power consumption modes in a substantiallyidentical fashion as that described above in relation to the operationof the control system 505. In response to sensed cardiovascular data bythe sensors 370, 372, the microprocessor 610 and the power supply 615may cooperate to deliver varying amounts of power to the flow restrictor360 and/or the sensors 370, 372, thereby conserving power when possible.Thus, the microprocessor 610 may lead the device 300 through a varietyof power consumption modes during which the sensors 370, 372 and theflow restrictor 360 function in a variety of active and inactive statessuited to the existing cardiovascular conditions of the patient, therebyconserving power when appropriate. This power consumption mode protocolmay prolong the service life of the power supply 615.

The device 300, and the various components thereof, may be manufacturedfrom a variety of materials, including, by way of non-limiting example,plastics, polytetrafluoroethylene (PTFE), polyether block amide (PEBAX),thermoplastic, polyimide, silicone, elastomer, shape memory materials,metals, such as stainless steel, titanium, shape-memory alloys such asNitinol, polymers, composite materials, and/or other biologicallycompatible materials. In addition, the device 300 may be manufactured ina variety of lengths, diameters, dimensions, and shapes to accommodate avariety of applications. The wall of the support body 600 is configuredto be sufficiently thin so as not to significantly restrict blood flowthrough the unactivated device 300. The outer diameter of the device 300may be varied so as to fit within a particular blood vessel and to adaptto different blood vessel sizes. Similarly, the length of the device 300may be varied according to anatomical and applicational need. Forexample, in one embodiment the support body 600 may be manufactured tohave length of about in the range of 2-5 cm. In another embodiment, thesupport body 600 of the device 300 may be manufactured to have atransverse dimension or diameter of about 5-8 mm, thereby permitting thedevice to be configured for insertion into the renal vasculature of apatient.

With general reference to FIGS. 7 a-9, schematic illustrations ofspecific embodiments of the intravascular flow-modifying device 300utilizing various power supply arrangements are shown. In mostinstances, each intravascular flow-modifying device is configured torestrict intravascular flow when the device is activated and powered.Conversely, when the device is inactivated or unpowered, the device isconfigured to allow as much flow as possible through the device whilestill maintaining an expanded condition within the vessel lumen. Aremote or local energy source may be physically or remotely coupled tothe intravascular flow-modifying device to provide energy to the powersupply (e.g., 615) of the device.

The design, function, and use of these specific embodiments, in additionto the control system 505 and the driver 520, are the same as describedwith reference to FIG. 6, unless otherwise noted or apparent from thedescription. In addition, any anatomical features illustrated in FIGS. 7a-9 are the same as discussed with reference to FIGS. 1 and 2, unlessotherwise noted. In each embodiment, the connections between theindividual components of the device (e.g., the microprocessor, thedriver, the communication module, the power supply, the sensors, and/orthe flow constrictor) may be physical (such as, by way of non-limitingexample, wires, tubes, cables, etc.) or remote (such as, by way ofnon-limiting example, wireless transmitter/receiver, inductive coupling,magnetic coupling, etc.). For physical connections, the connection maytravel intra-arterially, intravenously, subcutaneously, or through othernatural tissue paths.

As stated above, an energy source may be physically or remotely coupledto the intravascular flow-modifying device to provide energy to thedevice. As shown in FIG. 7 a, according to one embodiment of thedisclosure, an external energy source 670 may be directly coupled to anintravascular flow-modifying device 675 positioned within the bloodvessel 100 using an electrical cable or lead 680. The electrical cable680 may travel down a length of the blood vessel 100 before emergingthrough the vessel wall 120 to exit the patient's body through the skinS (e.g., at the insertion site for the device 675). In alternateembodiments, the cable 680 may exit through the vessel wall 120 to enteran adjacent vessel 685 before eventually exiting the patient's bodythrough the skin S. In some embodiments, the external energy source maybe coupled to and controlled by the control system 505 and/or the driver520 (shown in FIG. 5).

In addition to physical power connections, an energy source may bewirelessly coupled to the device to provide a remote means of supplyingenergy to the device. FIGS. 7 b-7 f schematically illustrate varioustypes of wireless energy transmission arrangements for use with any ofthe intravascular flow-modifying devices described herein. Various typesof energy may be supplied to the power source 625. The energy types mayinclude, for example, radio frequency (RF) energy, X-ray energy,microwave energy, acoustic or ultrasound energy such as focusedultrasound or high intensity focused ultrasound energy, light energy,electric field energy, magnetic field energy, combinations of the same,or the like. As mentioned above in relation to FIGS. 5 and 6, energy maybe delivered to the various components of the device continuously,periodically, episodically, or a combination thereof depending upon theparticular power consumption mode of the device at any given time.

FIG. 7 b illustrates an intravascular flow-modifying device 686positioned within the vessel 100. The device 686 includes an electrodecable or lead 688 that couples the device 686 to a receiving coilassembly 690, which may be implanted extravascularly within subcutaneoustissue (as shown) or intravascularly near the skin surface S (notshown). The receiving coil assembly 690 may include a receiving coil 692disposed on a flexible substrate 694. The receiving coil 692 may receiveenergy from an external energy source 670, such as, by way ofnon-limiting example, a transmitting coil, and then transmit the energyto through the cable 688 to the power supply 615 of the device 686.

FIG. 7 c illustrates an intravascular flow-modifying device 700configured for wireless power acquisition according to one embodiment ofthe present disclosure. The device 700 includes a receiving coilassembly 705 wrapped about an external surface 710 of the device 700.The receiving coil assembly 705 may be integrally formed with the device700, or may be movably attached to the device 700 to permit freeexpansion of the receiving coil assembly 705 with expansion of thedevice 700. The receiving coil assembly 705 may be shaped in the form ofa semi-cylinder as shown or in the form of a cylindrical sleeve (notshown). The receiving coil assembly includes a receiving coil 715 thatmay be connected to at least one (optional) electrode pad 720. The coil715 and the electrode pads 720 comprise a conductive metal disposed on aflexible substrate material 722. The metal may be laminated onto thesubstrate material 722, or the substrate 722 may be chemically etched todefine the coil 715 and the electrode pads 720. The coil 715 transfersreceived energy to the power supply 615 of the device 700. In someembodiments, the energy transfer may be transferred through theelectrode pad 720 to the power supply 615 or other components of thedevice 700 (not shown).

FIG. 7 d illustrates the intravascular flow-modifying device 700 in awireless transmission arrangement with an intravascular transmitterdevice 725 according to one embodiment of the present disclosure. Thedevice 700 is shown positioned in the vessel 100, which contains thebaroreceptors of interest. A transmitting device 725 may be positionedin an adjacent vessel 730 that lies in close proximity to the vessel100. In the pictured embodiment, the transmitting device 725 includes acoil assembly 735, which is similar to the construction and arrangementof assembly 705 disposed on device 700 as described previously, disposedon a stent-like tubular support structure 737. The transmitting device725 and the flow-modifying device 700 are positioned and anchored withintheir respective vessels such that their coil assemblies, 735 and 705,respectively, are arranged “face-to-face.”

In alternate embodiments, the transmitting device is implanted in thesubcutaneous tissue instead of within a vessel. In such embodiments, thetransmitting coil assembly may be disposed on a differently shapedsupport structure than the tubular support structure 737.

The coil assembly 735 may emit an RF or other electromagnetic signalpicked up by the coil assembly 705 on the intravascular flow-modifyingdevice 700. In some embodiments, the transmitting coil assembly 725 maybe under the control of the user and/or the control system 505. In someembodiments, the coil assembly 735 on the transmitting device 725 mayact as an antenna to wirelessly receive command signals and energy fromthe control system 505. The coil assembly 735 on the transmitting device725 may act as an antenna to wirelessly receive command signals from thecontrol system 505, or may be operably coupled to the control system 505(not shown) via physical cables or leads 738 which travel down thevessel 730 through the skin S. The transmitting device 725 is preferablydisposed in a venous vessel to reduce the risk of thromboembolism andstroke.

FIG. 7 e illustrates an intravascular flow-modifying device 740 in awireless transmission arrangement according to one embodiment of thepresent disclosure. The device 740 is shaped and configuredsubstantially identical to the device 700 except for the differencesnoted herein. The device 740 is shown positioned in the vessel 100,which contains the baroreceptors of interest. The device 740 includes atransmitter coil assembly 745, which is positioned on the externalsurface of the device 740 opposite to the receiver coil assembly 705.The transmitter coil assembly is similar to the construction andarrangement of assembly 705. The substantially “planar” receiver coilassembly 705 and the transmitter coil assembly 745 are positioned on thedevice 740 such that the assemblies are arranged “face-to-face.” In someembodiments, the transmitter coil assembly 745 may be under the controlof the user and/or the control system 505. In some embodiments, thetransmitter coil assembly 745 may be under the control of themicroprocessor 610. The transmitter coil assembly 745 may emit an RF orother electromagnetic signal picked up by the receiver coil assembly705.

FIG. 7 f illustrates an intravascular flow-modifying device 750 in awireless transmission arrangement according to one embodiment of thepresent disclosure. The device 750 includes an expandable support body760 shaped and configured as a helical receiver coil. The device 750 isshown positioned in the vessel 100, which contains the baroreceptors ofinterest. A helical transmitter coil 755 may be positioned in theadjacent vessel 730 that lies in close proximity to the vessel 100. Inthe pictured embodiment, the helical transmitter coil 755 is similar tothe construction and arrangement of the support body 760. The helicaltransmitter coil 755 and the helical flow-modifying device 750 arepositioned and anchored within their respective vessels such that theircoil axes are substantially aligned and/or are substantially parallel.The helical transmitter coil 755 may emit an RF or other electromagneticsignal picked up by the helical support body 760 of the intravascularflow-modifying device 700.

In some embodiments, the helical transmitter coil 755 may be under thecontrol of the user and/or the control system 505. In some embodiments,the helical transmitter coil 755 may act as an antenna to wirelesslyreceive command signals and energy from the control system 505. Thehelical transmitter coil 755 may act as an antenna to wirelessly receivecommand signals from the control system 505, or may be operably coupledto the control system 505 (not shown) via physical cables or leads 738which travel down the vessel 730 through the skin S. The helicaltransmitter coil 755 is preferably disposed in a venous vessel to reducethe risk of thromboembolism and stroke. Transmissions between thehelical transmitter coil 755 and the helical support body 760 may beused to power the device 750. For example, as current is run through thehelical transmitter coil 755, which may be coupled to the control system505 via the cable 738, an electromagnetic field may be produced thatinduces a current in the helical support body 760. Such induced currentmay be harnessed by the power supply 615 (not shown) within the device750 to charge the power supply 665 (not shown) or to directly powerother individual components of the device 750. The size of the coils andthe number of turns in each helical structure may determine the amountof energy delivered.

In alternate embodiments, as shown in FIGS. 8 a-9, the intravascularflow-modifying device itself may be shaped and configured to generateenergy in cooperation with the cardiovascular activity within thepatient's body.

For example, FIG. 8 a illustrates an intravascular flow-modifying device770 according to one embodiment of the present disclosure. The device770 is positioned within the vessel 100 such that blood flows from theupstream area 380, through a lumen 775 of the device 770, and into thedownstream area 385. In this embodiment, the vessel 100 comprises anarterial vessel. The device 770 may include a hollow, cylindricalgenerator 775 housed within a hollow, cylindrical support body 780. Thegenerator 775 includes a central body portion 781, a toroidal ring 785,and a toroidal ring 787. The central body portion 781 comprises aspring-like elongate, hollow cylinder formed of a plurality ofelectrically conductive wires 782. The ring 785 and the ring 787 aredisposed at proximal and distal ends 788, 789, respectively, of thedevice 770. In the pictured embodiment, the ring 785 comprises anannular mass that is shaped and configured to have significantly moremass than the ring 787. The device 770 is anchored within the vessel 100in the region of the ring 787. The rings 785, 787 may be magnetized, andmay be formed of any of a variety of biocompatible materials, including,by way of non-limiting example, magnetic, ferromagnetic, paramagnetic,and/or non-magnetic materials.

The intravascular flow-modifying device 770 employs the principle ofvariable distance capacitance to generate energy, wherein the bodyportion 781 comprises a variable distance capacitor. As the patient'sheart contracts, a pulse of blood contacts the proximal end 788 beforetravelling through the lumen 775 of the device 770. As shown in FIG. 8b, the proximal end 788 may be shaped and configured such that when theblood contacts the proximal end 788, the ring 785 is shifted toward theportion 787, thereby compressing the body portion 781 within the supportbody 780 and causing the conductive wires 782 to move closer to oneanother. As the patient's heart expands in preparation for the nextbeat, the decrease in intra-arterial pressure allows the body portion781 to re-expand and the portion 785 to shift away from the portion 787.With each beat of the patient's heart, this cycle of compression andexpansion of the body portion 781 sequentially repeats to transformkinetic energy into electrical energy (or current) within the bodyportion 781. The generated current may be harnessed by the power supply615 (not shown for the sake of simplicity) within the device 770 tocharge the power supply 665 (not shown for the sake of simplicity) or todirectly power other individual components of the device 770.

FIG. 9 illustrates another intravascular flow-modifying device 790shaped and configured to generate energy in cooperation with thecardiovascular activity within the patient's body according to oneembodiment of the present disclosure. The device 790 includes a lumen791 that contains a proximal fluid area 792, a distal fluid area 793, aflow restrictor 360, and a generator device 794. The device 790 includesa proximal end 795 and a distal end 796. The device 790 is positionedwithin the vessel 100 and the generator device is operatively disposedwithin the lumen 791 such that blood flows from the upstream area 380,through the proximal fluid area 792, through the generator device 794,through the distal fluid area 793, and into the downstream area 385. Thegenerator device 794 may comprise an electrical generator that, ingeneral, utilizes the mechanical energy associated with the movement ofblood through the generator device 794 to generate electricity forpowering the device 790. As fluid flows from the proximal fluid area 792to the distal fluid area 793 through the generator device 794,electrical energy is generated.

The present disclosure contemplates the use of any suitable generatordevice 794 for use within the device 790 to accommodate particularneeds. For example, the generator 794 may comprise a turbine mechanismthat, in response to the propulsion of blood through the generatordevice 794 generated by the patient's own cardiovascular system (e.g.,cardiac and vascular contractions and/or blood pressure changes),converts the kinetic energy of the blood into electric energy to chargethe power supply 615 (not shown). In particular, as blood flows throughthe turbine mechanism, the turbine mechanism may be configured to rotatea conductive coil through a magnetic field created by opposing magneticstructures (e.g., magnetic rings located at the proximal and distal ends795, 796, respectively, of the device 790) to induce an electric currentin the conductive coil. The generated current may be harnessed by thepower supply 615 (not shown) within the device 790 to charge the powersupply 665 (not shown) or to directly power other individual componentsof the device 790.

In addition, micro-electrical-mechanical systems (MEMS) technology mayprovide various generators 794 for use in embodiments of the currentdisclosure. In some embodiments, the flow restrictor 360 of the device790 may function as the generator device or may be integrally coupled tothe generator device.

With general reference to FIGS. 10 a-15 b, schematic illustrations ofspecific embodiments of the intravascular flow-modifying device 300 areshown. As mentioned above, in general, each embodiment of the presentdisclosure is configured to restrict intravascular flow when the deviceis activated and powered. Conversely, when the device is inactivated orunpowered, the device is configured to allow as much flow as possiblethrough the device while still maintaining an expanded condition withinthe vessel lumen. Specifically, each activated intravascularflow-modifying device indirectly modulates the baroreceptor system byrestricting flow and creating back pressure upstream of the device,thereby artificially increasing the blood pressure upstream of thedevice to affect the baroreceptor system (either by deforming the vesselwall located immediately upstream of the intravascular flow-modifyingdevice to activate baroreceptors and/or by increasing intrarenalperfusion and pressure to decrease baroreceptor-mediated sympatheticactivity).

The design, function, and use of these specific embodiments, in additionto the control system 505 and the driver 520, are the same as describedwith reference to device 300 in FIG. 6 a, unless otherwise noted orapparent from the description. In addition, any anatomical featuresillustrated in FIGS. 10 a-15 b are the same as discussed with referenceto FIGS. 1 and 2, unless otherwise noted. In each embodiment, theconnections between the individual components of the device (e.g., themicroprocessor, the driver, the communication module, the power supply,the sensors, and/or the flow constrictor) may be physical (such as, byway of non-limiting example, wires, tubes, cables, etc.) or remote (suchas, by way of non-limiting example, wireless transmitter/receiver,inductive coupling, magnetic coupling, etc.). For physical connections,the connection may travel intra-arterially, intravenously,subcutaneously, or through other natural tissue paths.

FIGS. 10 a-10 c illustrate an intravascular flow-modifying device 800positioned within the vessel 100. The device 800 includes a flowrestrictor 805 positioned centrally within a lumen 806 of an elongate,hollow, cylindrical support body 807. The device 800 includes a proximalend 810 and a distal end 812. The device 800 is shaped and configuredfor intravascular placement in a vessel such that the proximal end 810is positioned upstream to the distal end 812, and blood flows from theintravascular area 380 proximal to the device 800, through proximal end810, through the flow restrictor 805, and out the distal end 812 intothe intravascular area 385 distal to the device 800. The flow restrictor805 includes a pivotable disc 814 having a central aperture 816 and sidetabs 818. The side tabs 818 pivotably anchor the disc 814 within thesupport body 807 such that the disc 814 may pivot from an activeposition (as shown in FIG. 10 a) to a less active (as shown in FIG. 10b) or inactive position (as shown in FIG. 10 c).

The aperture 816 permits blood flow through the device 800 even when theflow restrictor 805 is in an active condition. In some embodiments, thedisc may include several perforations or apertures to permit sufficientblood flow through the device 800 even when the flow restrictor 805 isin an active condition. For example, FIG. 10 d illustrates across-section of a device 800′ comprising a disc 814′ having a pluralityof peripheral apertures 819 in addition to a central aperture 816′.

The device 800 further includes an actuator 820 that couples the disc814 to a driver 822, which provides energy to the actuator 820 andenables the actuator 820 to pivot the disc 814 through several degreesof activation (i.e., degrees of occlusion of the lumen 806). Theactuator 820 and the driver 822 are positioned on one side of the flowrestrictor 805. In the pictured embodiment, the actuator 820 and thedriver 822 are positioned closer to the proximal end 810 than the distalend 812. In other embodiments, the actuator 820 and the driver 822 maybe positioned on an opposite side of the flow restrictor 805, with theactuator 820 and the driver 822 positioned closer to the distal end 812than the proximal end 810. As shown in FIG. 10 c, in alternateembodiments, the device 800 may include a plurality of actuators anddrivers positioned on both sides of the flow restrictor 805. In FIG. 10a, the actuator 820 extends along a longitudinal axis LA of the actuator820 from the driver 822 to a position 824 located along an axis VA on aproximal face of 826 of the disc 814. In some embodiments, the axis LAalso corresponds to the longitudinal axis of the device 800. The axis VAis substantially perpendicular to the axis LA.

The actuator 820 is shaped and configured as a linear actuator thatshifts along the axis LA to transition the disc 814 through variousdegrees of activation. In the pictured embodiment, the actuator 820 isshaped and configured as an elongate rod that extends from the driver822 to the disc 814. The actuator 820 may be any of a variety of linearactuators capable of applying a mechanical force to the disc 814 to tiltthe disc 814 around the axis HA, including, but not limited to, a rod, acoil, a spring, and/or a lever. The actuator 820 may be formed of, byway of non-limiting example, a metallic material such as titanium orstainless steel, an elastomeric material, a polymeric material, a rubbermaterial, a composite material, a shape memory material, a dielectricelastomer, a magnetic material, an electrostatic acrylic elastomer, orany other suitable flexible material to facilitate transitioning of thedisc 814 between the active and inactive conditions. For example, in thepictured embodiment, the actuator 820 is formed of the shape-memoryalloy Nitinol, which exhibits superelastic characteristics thatfacilitate applying mechanical force to the disc 814 to pivot it throughvarious degrees of activation.

The disc 814 pivots within the device 800 about the axis HA in responseto a mechanically induced force that is provided via selective actuationof the actuator 820 by the driver 800. Depending upon the signals andpower received from other components of the device 800 (e.g., amicroprocessor and/or power supply), the driver 822 influences theactuator 820 to appropriately tilt the disc 814 within the lumen 806about an axis HA, which is substantially perpendicular to the axis VA.In FIG. 10 a, the flow restrictor 805 is shown in an active condition,with a planar surface of the disc 814 being substantially planar to theaxis VA. When the flow restrictor 805 is in an active condition, bloodflow through the device 800 is partially blocked by the disc 814, andblood flow volume and flow rate through the device 800 is reduced,thereby creating a back pressure in the intravascular area 380 thatactivates the baroreceptors encircling the area 380.

When the driver 822 is signaled to shift the flow restrictor 805 into aless active condition, as shown in FIG. 10 b, the driver 822 causes theactuator 820 to lengthen, thereby causing the position 824 of the disc814 to tilt about the axis HA away from the driver 822 and the proximalend 810. As the flow restrictor tilts into a less active condition(i.e., as the disc 814 tilts away from the axis VA toward the axis HA),the amount of intraluminal occlusion decreases to allow blood to flow atan increased volume and rate through the device 800. This decrease inintraluminal occlusion relieves the back pressure in the area 380,thereby decreasing the activity of baroreceptor signaling in the area380.

When the driver 822 is signaled to shift the flow restrictor 805 into aninactive condition, as shown in FIG. 10 c, the drivers 822 cause theactuators 820 to lengthen sufficiently to cause the disc 814 to tiltuntil a planar surface (e.g., the proximal face 826) of the disc 814 issubstantially aligned with and planar to the axis HA. When the flowrestrictor 805 tilts into an inactive condition (i.e., as the disc 814tilts away from the axis VA toward the axis HA), intraluminal occlusionis significantly minimized. Thus, when the flow restrictor 805 is in aninactive condition, blood flows through the lumen 806 of the device 800with minimal disruption in blood volume and flow rate.

Conversely, when the driver 822 is signaled to shift the flow restrictor805 into a more active condition, as shown in FIG. 10 a, the driver 822causes the actuator 820 to shorten, thereby causing the position 824 ofthe disc 814 to tilt about the axis HA away from the distal end 812 andtoward the driver 822 and the proximal end 810. As the flow restrictortilts into a more active condition (i.e., as the disc 814 tilts awayfrom the axis HA toward the axis VA), the amount of intraluminalocclusion increases and blood flows at a decreased volume and ratethrough the device 800.

As mentioned above with reference to FIG. 10 a, the side tabs 818pivotably anchor the disc 814 within the support body 807 such that thedisc 814 may pivot from an active position (as shown in FIG. 10 a) to aless active (as shown in FIG. 10 b) or inactive position (as shown inFIG. 10 c). FIGS. 11 a-11 c illustrate one possible embodiment of thepivoting relationship between the disc 814, the side tabs 818, and thesupport body 807. As indicated in FIG. 11 a, the support body 807 formsa hollow, generally cylindrical tube that houses the disc 814. Thesupport body 807 may include thickened portions 827, which contain apair of opposed recesses 828 for receiving the side tabs 818. Eachrecess 828 is a mirror image of the other. Each recess 828 is positionedalong the axis HA within the luminal surface of one of the portions 827.

The contour and placement of the recesses 828 is selected to limit therange of movement of the side tabs 818 and the disc 814 between anactive position (as illustrated in FIG. 11 b) and an inactive position(as illustrated in FIG. 11 c). Preferably, the recesses 828 have asloped or curved circumferential edge 829 to facilitate the movement ofblood through the recess and prevent stagnation of blood flow within therecess. Preferably, the recesses 828 also provide a curved or arcuateinner surfaces 830 for contact with the side tabs 818. Preferably, theside tabs 818 include correspondingly curved or arcuate outer surfaces831 for contact with the inner surfaces 830. Preferably, the disc 814includes curved or arcuate outer surfaces 832 for contact with the innersurfaces 830. By providing curved and arcuate edges on the recess edges829, the side tabs 818, and the disc 814, blood flowing past the flowrestrictor 805 may be less likely to experience flow disturbance,stagnation, or high shear stress (and platelet activation) along theedges of the flow restrictor 805 and the recesses 828. Thus, the risk ofplatelet aggregation and thrombus formation around the flow restrictor805 may be reduced.

FIG. 11 b illustrates the side tab 818 positioned within a recess 828such that the disc 814 (and thus the flow restrictor 805) is in anactive condition, reducing blood flow and flow rate through the device800 to activate baroreceptors proximal to the device 800. Each recess828 is shaped and configured to provide active stops 833 and inactivestops 834. The active stops 833 cooperate with the actuator 829 toprevent the side tab 818 (and thus the disc 814) from pivoting past afully active position and/or spinning from the mechanical force of bloodtravelling through the device 800.

FIG. 11 c illustrates the side tab 818 positioned within a recess 828such that the disc 814 (and thus the flow restrictor 805) is in aninactive condition, allowing (and perhaps minimally reducing) blood flowand flow rate through the device 800 and relieving any intraluminal backpressure proximal to the device 800. The inactive stops 834 cooperatewith the actuator 829 to prevent the side tab 818 (and thus the disc814) from pivoting past a fully inactive position and/or spinning fromthe mechanical force of blood travelling through the device 800.

FIGS. 12 a-12 c illustrate an intravascular flow-modifying device 850positioned within the vessel 100. The device 850 is shaped andconfigured substantially identical to the intravascular flow-modifyingdevice 800 except for the differences noted herein. The device 850includes a flow restrictor 855 positioned centrally within a lumen 806and between the proximal end 810 and the distal end 812 of the elongate,hollow, cylindrical support body 807. The device 850 also includes aplurality of drivers 822 and actuators 820 coupled to the flowrestrictor 855. The device 850 is shaped and configured forintravascular placement in a vessel such that the proximal end 810 ispositioned upstream to the distal end 812, and blood flows from theintravascular area 380 proximal to the device 850, through proximal end810, through the flow restrictor 855, and out the distal end 812 intothe intravascular area 385 distal to the device 850.

The flow restrictor 855 includes a plurality of pivotable, concentric,circular rings 856 that gradually decrease in diameter from the outsidering 858 to the center ring 860. The center ring 860 includes a centralaperture 862, and the outside ring 858 includes side tabs 864. The sidetabs 864 are substantially identical to the side tabs 818 except for thedifferences noted herein. In the pictured embodiment, the flowrestrictor 855 includes two rods 866, each of which extends from a sidetab 864 through the plurality of concentric rings 856 to the centralaperture 862. In some embodiments, the flow restrictor 855 may includeonly one rod that extends from one side tab 864, through the concentricrings 856 and the central aperture 862, to the other side tab 864. Theside tabs 864 and the rods 866 pivotably anchor the plurality ofconcentric rings 856 within the support body 807 such that theconcentric rings 856 may individually pivot about the rods 866 from anactive position (as shown in FIG. 12 a) to a less active (as shown inFIG. 12 b) or inactive position (as shown in FIG. 12 c).

The actuators 820 are shaped and configured as linear actuators thatshift in a plane substantially parallel to an axis LA of each actuator820 to transition the flow restrictor 855 through various degrees ofactivation. Each individual actuator 820 is coupled to a correspondingconcentric ring 856 and a corresponding driver 822. Though the device850 is shown including each individual driver 822 coupled to anindividual actuator 820-ring 856 pair, other embodiments may include anynumber and combination of actuators, drivers, and rings. In FIG. 12 a,each actuator 820 extends along the longitudinal axis LA from thecorresponding driver 822 to a position 868 located on a proximal face of870 of a concentric ring 856. Each individual concentric ring 856 maypivot within the device 850 about the axis HA in response to amechanically induced force that is provided via selective actuation ofthe corresponding actuator 820 by the corresponding driver 800.Depending upon the signals and power received from other components ofthe device 850 (e.g., a microprocessor and/or power supply), variousdrivers 822 influence the corresponding actuators 820 to appropriatelytilt particular rings 856 within the lumen 806 about the axis HA and/orthe rods 866.

In FIG. 12 a, the flow restrictor 855 is shown in an active condition,with the planar surfaces of the all the concentric rings 856 beingsubstantially planar to the axis VA. When the flow restrictor 855 is inan active condition, blood flow through the device 800 is partiallyblocked by the plurality of concentric rings 856, and blood flow volumeand flow rate through the device 850 is reduced, thereby creating a backpressure in the intravascular area 380 that activates the baroreceptorsencircling the area 380. When the drivers 822 are signaled to shift theflow restrictor 855 into an active condition, the drivers 822 cause thecorresponding actuators 820 to shorten, thereby causing the position 868of the corresponding ring 856 to tilt about the axis HA away from thedistal end 812 and toward the proximal end 810. As the flow restrictor855 tilts into a more active condition, the amount of intraluminalocclusion increases and blood flows at a decreased volume and ratethrough the device 850.

When some drivers 822 are signaled to shift the flow restrictor 855 intoa less active condition, as shown in FIG. 12 b, the appropriate drivers822 cause the corresponding actuators 820 to lengthen, thereby causingthe positions 868 of the corresponding rings 856 to tilt about the axisHA away from the proximal end 810. As the flow restrictor tilts into aless active condition, the amount of intraluminal occlusion decreases toallow blood to flow at an increased volume and rate through the device850. This decrease in intraluminal occlusion relieves the back pressurein the area 380, thereby decreasing the activity of baroreceptorsignaling in the area 380.

When some drivers 822 are signaled to shift the flow restrictor 855 intoan inactive condition, as shown in FIG. 12 c, the appropriate drivers822 cause the corresponding actuators 820 to lengthen sufficiently tocause the corresponding rings 856 to tilt until a planar surface (e.g.,the proximal face 870) of the ring 856 is substantially aligned with andplanar to the axis HA. When the flow restrictor 855 tilts into aninactive condition, intraluminal occlusion is significantly minimized.Thus, when the flow restrictor 855 is in an inactive condition, bloodflows through the lumen 806 of the device 850 with minimal disruption inblood volume and flow rate.

FIGS. 13 a-13 b illustrate an intravascular flow-modifying device 880positioned within the vessel 100. The device 880 includes a flowrestrictor 882 housed within the elongate, hollow, cylindrical supportbody 881. The device 880 includes a proximal end 810 and a distal end812. The device 880 is shaped and configured for intravascular placementin a vessel such that the proximal end 810 is positioned upstream to thedistal end 812, and blood flows from the intravascular area 380 proximalto the device 880, through proximal end 810, through the flow restrictor882, and out the distal end 812 into the intravascular area 385 distalto the device 880.

The flow restrictor 882 includes a proximal ring 884, which is shapedand configured to rotate within the support body 881, a distal ring 886,which is shaped and configured to be stationary within the support body881 (as indicated by the dashed lines 888), a plurality of rods 890, abearing ring 891, which is configured to be stationary within theproximal ring 884 (as indicated by the dashed lines 893), and an innersheath 895, which defines an inner lumen 897 of the device 880. Thedistal ring 886 anchors the flow restrictor 882 within the support body881 such that the proximal ring 884 may rotate to transition the flowrestrictor 882 from an inactive position (as shown in FIG. 13 a) to amore active position (as shown in FIG. 13 d). The plurality of rods 890extend from the proximal ring 884 through aligned openings 892 in thedistal ring 886 and cooperate with the proximal ring 884 and the distalring 886 to selectively restrict blood flow through the device 880.

While the flow restrictor 882 is in an inactive condition, as shown inFIG. 13 a, the rods 890 are positioned between the rings 884, 886 suchthat they pass in directions parallel to and spaced a given distance Rfrom a longitudinal axis A-A of the flow restrictor 882 extendingthrough the rings 884, 886. The rods 890 extend through the openings 892in the distal ring 886 and terminate in rounded or curved distal ends894 that lack sharp angles so as to minimize the potential forthrombogenesis and/or turbulent flow within the vessel 100. The proximalends 896 (not shown) of the rods 890 are coupled to the proximal ring884 by multi-axial joints 898, which permit the rods 890 to twist and/ortilt with respect to the axis A-A and a plane P of the rings 884, 886(that is substantially perpendicular to the axis A-A). The rods 890 maybe made of any of a variety of semi-rigid or rigid biocompatiblematerials, including, by way of non-limiting example, stainless steel,titanium, aluminum, polymeric composites, and/or plastic. The joints 898may be any one of a variety of joint types, including, by way ofnon-limiting example, ball-and-socket joints and/or multi-axial screwjoints.

The bearing ring 891 is positioned within the proximal ring 884 andsupports the ring 884 for rotation in the plane P. The bearing ring 891is shaped and configured to be stationary as the flow restrictortransitions from inactive to active (and visa-versa) conditions (asindicated by the dashed lines 902).

The inner sheath 895 extends from the bearing ring 891 to the distalring 886 and separates the blood flowing through the device 880 from alength of the rods 890 positioned between the rings 884, 886. The innersheath 895 is shaped and configured as a flexible, hollow, cylindricaltube that defines the lumen 897 of the device 880. The inner sheath 895permits blood flow through the device 880 even when the flow restrictor882 is in an active condition (as shown in FIG. 13 d). In someembodiments, as illustrated in FIGS. 13 b and 13 c, the inner sheath 895may comprise a continuous extension of the support member 881, whereinthe inner sheath 895 and the support member 881 form a hollow, generallytoroidal structure 899 encasing the flow restrictor 882 and separatingthe flow restrictor 882 from the bloodstream.

As illustrated in more detail in FIGS. 13 b and 13 c, the device 880further includes an actuator 900 that couples the proximal ring 884 to adriver 902, which provides energy to the actuator 900 and enables theactuator 900 to rotate the proximal ring 884 through several degrees ofactivation (i.e., degrees of occlusion of the vessel 100). The actuator900 and the driver 902 are substantially identical to the aforementionedactuator 820 and driver 822, respectively, unless otherwise disclosedherein. In the pictured embodiment, the actuator 900 and the driver 902are positioned adjacent to the proximal ring 884 and within the toroidalstructure 899. In other embodiments, the actuator 900 and the driver 902may be elsewhere within the device 880, such as, by way of non-limitingexample, within the lumen 897 against the inner sheath 895. In alternateembodiments, the device 880 may include a plurality of actuators andcorresponding drivers.

The proximal disk 884 rotates within the toriodal structure 889 aboutthe axis A-A in response to a mechanically induced force that isprovided via selective actuation of the actuator 900 by the driver 902.Depending upon the signals and power received from other components ofthe device 880 (e.g., a microprocessor and/or power supply), the driver902 influences the actuator 900 to appropriately rotate the proximaldisk 884 to restrict blood flow through the lumen 897 of the device 880.As described in further detail below with respect to FIG. 13 d, rotationof the proximal ring 884 from an inactive position to an active positioncauses restriction and occlusion of the lumen 897 of the device 880.

The actuator 900 may be any of a variety of actuators capable ofapplying a mechanical force to the proximal ring 884 to rotate the ring884 around the axis A-A, including, but not limited to, a gear, a rod, acoil, a spring, and/or a lever. The actuator 900 may be formed of, byway of non-limiting example, a metallic material such as titanium orstainless steel, an elastomeric material, a polymeric material, a rubbermaterial, a composite material, a shape memory material, a dielectricelastomer, a magnetic material, an electrostatic acrylic elastomer, orany other suitable flexible material to facilitate transitioning of theflow restrictor 882 between the active and inactive conditions.

For example, in the embodiment pictured in FIG. 13 b, the actuator 900is shaped as a circular pinion gear configured to meshingly engage withthe proximal ring 884. In the pictured embodiment, the actuator 900 ispreferably formed of a rigid or semi-rigid metal, polymer, or compositematerial, such as, by way of non-limiting example, titanium and/orstainless steel. When the driver 902 powers the actuator 900 to rotatein a first direction, the rotation of the actuator 900 impels therotation of the proximal ring 884 in a second direction that is oppositeto the first direction.

In the embodiment pictured in FIG. 13 c, the actuator 900 is shaped asan elongate rod or cable configured to fixedly attach to a position 904on the proximal ring 884. The actuator 900 is shaped and configured toextend along a longitudinal axis LA of the actuator 900 from the driver902 to the position 904 on the ring 884. In the pictured embodiment, theactuator 900 may be formed of a self-expanding biocompatible material,such as Nitinol, a resilient polymer, a dielectric elastomer, an acrylicelastomer, or an elastically compressed spring temper biocompatiblematerial. Other materials having shape memory characteristics, such asparticular metal alloys, may also be used. When the driver 902 powersthe actuator 900 to shift the proximal ring 884 into a more activeposition, the actuator 900 shortens along the axis LA, thereby shiftingthe position 904 toward to driver 902 and rotating the proximal ring 884into a more active position.

FIG. 13 d illustrates the intravascular flow-modifying device 880 in anactive condition, wherein the proximal ring 884 is rotated into anactive position, thereby decreasing the cross-sectional areas anddiameters along the length of the lumen 897 and restricting blood flowthrough the device 880. FIG. 13 d shows the effect of rotating theproximal ring 884 through a given angle as indicated by the curvedarrow. Essentially, this rotation of the ring 884 twists the rods 890and retracts them through the openings 892 in the distal ring 886. Asthe rods 890 retract through the openings 892, the ends 894 prevent therods 890 from completely withdrawing from the ring 886. As a consequenceof the rods 890 twisting, the given radial distance R (described in FIG.13 a) is decreased. Specifically, centers of the rods 890 move radiallyinward to reduce the passage area through the lumen 897 of the device882. When the flow restrictor 882 is in an active condition, blood flowthrough the device 880 is delayed or partially blocked by the reducedpassage size of the lumen 897, and blood flow volume and flow ratethrough the device 880 is reduced, thereby creating a back pressure inthe intravascular area 380 that activates the baroreceptors encirclingthe area 380.

When the proximal ring 884 is returned to its original, inactiveposition (i.e., rotated back through the same given angle) as shown inFIG. 13 a, then the rods 890 will expand outwardly to provide amaximum-sized passage through the lumen 897 of the device 880. Forexample, with reference to FIGS. 13 c and 13 a, when the driver 902 issignaled to shift the flow restrictor 882 into a less active condition,the proximal ring 884 rotates about the axis A-A away from the driver902. As the flow restrictor 882 twists into a less active condition, theamount of intraluminal occlusion decreases to allow blood to flow at anincreased volume and rate through the lumen 897 of the device 880. Thisdecrease in intraluminal occlusion relieves the back pressure in thearea 380, thereby decreasing the activity of baroreceptor signaling inthe area 380. When the flow restrictor 882 is in an inactive condition,as shown in FIG. 13 a, blood flows through the lumen 897 of the device880 with minimal disruption in blood volume and flow rate.

FIGS. 14 a-14 b illustrate an intravascular flow-modifying device 920positioned within the vessel 100. FIG. 14 a illustrates the device 920in an active condition and FIG. 14 b illustrates the device 920 in aninactive or less active condition. The device 920 includes a flowrestrictor 922 housed within an elongate, hollow, cylindrical supportbody 924. The device 920 includes a lumen 925 that extends from aproximal end 810 to a distal end 812. The device 920 is shaped andconfigured for intravascular placement in a vessel such that theproximal end 810 is positioned upstream to the distal end 812, and bloodflows from the intravascular area 380 proximal to the device 920,through the proximal end 810, through the flow restrictor 922, and outthe distal end 812 into the intravascular area 385 distal to the device920.

The flow restrictor 922 includes an expandable balloon 926 that is influid communication with a driver 928 by means of a hollow flow line930. The driver 928 is shaped and configured as a pump to deliver afluid or a gas through the flow line 930 into a hollow chamber 932housed within the balloon 926. The driver pump 928 is configured tocommunicate with the communication module, microprocessor, and powersupply of the device 920 in substantially an identical manner as therespective components of the device 300. Thus, in response to theappropriate command signals, the driver pump 928 may deliver aninflation medium, whether a fluid or a gas, through the flow line 930into the chamber 932 to inflate the balloon 926 and transition the flowrestrictor 922 (and the device 920) from an inactive condition (as shownin FIG. 14 b) to a more active condition (as shown in FIG. 14 a), and todeflate the balloon 926 and transition the flow restrictor 922 back to aless active or inactive condition (as shown in FIG. 14 b).

In the pictured embodiment, the driver pump 928 and the fluid line 930are embedded within the support body 924. In other embodiments, thedriver 928 and the fluid line 930 may be positioned elsewhere within thedevice 920, such as, by way of non-limiting example, within the lumen925 or within the expandable balloon 926. In alternate embodiments, thedevice 920 may include a plurality of actuators and corresponding driverpumps. In the pictured embodiment, the driver pump 928 includes areservoir (not shown) containing the inflation medium. In otherembodiments, the driver pump may be coupled to a separate reservoir ofinflation medium positioned either within the device 920 or remote fromthe device 920.

In FIGS. 14 a and 14 b, the expandable balloon 926 is shaped andconfigured to have a generally annular and toroidal geometry including acentral passageway 934. In the pictured embodiment, the centralpassageway 934 defines the lumen 925 of the device 920. The balloon 926may include an interior surface 936 and a generally cylindrical exteriorsurface 938, which is circumferentially coupled to an entire innercircumference of the support body 924. In other embodiments, the balloon926 may be shaped and configured to have a semi-spherical orsemi-elliptical shape that resides on a portion of the support body 924instead of the entire inner circumference of the support body 924. Insuch embodiments, multiple balloons may be utilized to provide greaterdegrees of occlusion of the lumen 925 of the device 920. However shapedand configured, the expandable balloon is shaped and configured to lacksharp angles so as to minimize the potential for thrombogenesis and/orturbulent flow within the vessel 100.

Depending upon the signals and power received from other components ofthe device 920 (e.g., a microprocessor, communication module, and/orpower supply), the driver pump 928 appropriately inflates or deflatesthe balloon 926 to restrict or allow, respectively, blood flow throughthe lumen 925 of the device 920. When the driver pump 928 suppliesinflation media to the chamber 932 of the balloon 926, the balloon 926circumferentially expands or inflates, thereby transitioning the flowrestrictor 922 into an active condition by narrowing the lumen 925, asshown in FIG. 14 a. Narrowing the lumen 925 decreases thecross-sectional areas and diameters along the length of the lumen 925and decreases the blood flow volume and rate through the device 920,which creates a back pressure in the area 380 proximal to the device 920and activates the baroreceptors in the vicinity of area 380. It isimportant to note that the chamber 932 and the balloon 926 areconfigured to expand only to the extent that the flow restrictor 922permits blood flow through the central passageway 934 even when the flowrestrictor 922 is in an active condition.

When the driver pump 928 withdraws the inflation medium from the chamber932, the balloon 926 is returned to its original, inactive conditionwith the interior surface 936 drawn towards the exterior surface 938 asshown in FIG. 14 b. As the flow restrictor 922 transitions into a lessactive condition, the amount of intraluminal occlusion decreases toallow blood to flow at an increased volume and rate through the lumen925 of the device 920. This decrease in intraluminal occlusion relievesthe back pressure in the area 380, thereby decreasing the activity ofbaroreceptor signaling in the area 380. When the flow restrictor 922 isin an inactive condition, as shown in FIG. 14 b, blood flows through thelumen 925 of the device 920 with minimal disruption in blood volume andflow rate.

FIGS. 15 a-15 b illustrate an intravascular flow-modifying device 950positioned within the vessel 100. FIG. 15 a illustrates the device 950in an inactive condition and FIG. 15 b illustrates the device 920 in anactive condition. The device 950 includes a flow restrictor 952 housedwithin an elongate, hollow, cylindrical support body 954. The device 950includes a lumen 955 that extends from a proximal end 810 to a distalend 812 of the device 950. The device 950 is shaped and configured forintravascular placement in a vessel such that the proximal end 810 ispositioned upstream to the distal end 812, and blood flows from theintravascular area 380 proximal to the device 950, through the proximalend 810, through the flow restrictor 952, and out the distal end 812into the intravascular area 385 distal to the device 950.

The flow restrictor 952 includes at least one expandable structure 956and at least one corresponding biasing member 958 that is configured tobias the expandable structure 956 away from the walls of the supportbody 954 toward the center of the lumen 955. The expandable structure956 includes a first electrode 960, a polymeric film 962, and a secondelectrode 964. In the pictured embodiment, the device 950 includes atleast two expandable structures 956 and at least two correspondingbiasing members 958. In other embodiments, the flow restrictor mayinclude any number of expandable structures and corresponding biasingmembers.

The biasing member 958 provides sufficient force to the expandablestructure 956 to compel the expandable structure 956 to expand away fromthe support body 954 toward the lumen 955. In FIGS. 15 a and 15 b, thebiasing member 958 is schematically depicted as a generic structurepositioned adjacent the expandable structure 956 and within the supportbody 954. In various embodiments, the biasing member may be shaped andconfigured as any of a variety of biasing apparatuses, including, by wayof non-limiting example, a spring, a stationary projection or series ofprojections extending from the support body 954 toward the lumen 955,and/or light pressure from a fluid/gas diaphragm (as described abovewith respect to FIGS. 14 a and 14 b). Other embodiments may lack abiasing member. For example, the expandable structure 95 may be shapedand configured to self-bias and expand in the appropriate direction,thus obviating the need for a separate biasing member 958.

The expandable structure 956 is shaped and configured as anelectroactive polymer called a dielectric elastomer, which includes thefirst electrode 960 and the second electrode 962 sandwiched around thepolymeric film 964. The polymeric film 964 extends beyond the electrodes960, 962 to couple the expandable structure 956 to the support body 954at the margins 966 of the expandable structure 956. The expandablestructure includes an active area 968 that includes the electrodes 960,962 and extends between the margins 966. The active area 968 deflectsfrom the support body 954 when the flow restrictor 952 is in an activecondition to restrict the lumen 955 of the device 950. The electrodes960, 962 comprise compliant electrodes made of any of a variety ofsuitable materials, such as, by way of non-limiting example, carbonparticles suspended in a soft polymer matrix. The electrodes 960, 962are electrically coupled to the power supply (e.g., 615, not shown herefor the sake of simplicity) and/or a driver (e.g., 605, not shown herefor the sake of simplicity). In response to the appropriate commandsignals and/or power supply, the expandable structure 956 is activated(i.e., energized) to expand the active area and transition the flowrestrictor 952 (and the device 950) from an inactive condition (as shownin FIG. 15 a) to a more active condition (as shown in FIG. 15 b), anddeactivated to unexpand the active area and transition the flowrestrictor 952 back to an inactive condition.

It is important to note that the expandable structure 956 may convertbetween electrical energy and mechanical energy bi-directionally. Forexample, the expandable structure 956 may comprise an electricalgenerator because the expandable structure is configured to produce achange in electric field in response to deflection of the expandablestructure. Specifically, the change in electric field, along withchanges in the polymer dimension in the direction of the field, producesa change in voltage, and hence a change in electrical energy. Whendeflection of the active area 968 toward the support body 954 causes thenet area of the active area 968 to decrease and there is a charge on theelectrodes 960, 962, the active area 968 acts as a generator byconverting mechanical energy into electrical energy. Conversely, whenthe deflection away from the support body causes the net area of theactive area 968 to increase and charge is on the electrodes, the activearea 968 acts as an actuator by converting electrical energy tomechanical energy. The change in area in both cases corresponds to areverse change in the thickness T of the active area 968, i.e., thethickness T contracts when the planar area expands (as shown in FIG. 15b), and the thickness expands when the planar area contracts (as shownin FIG. 15 a). Thus, devices of the present disclosure may include bothactuator/mechanical and generator modes, depending on how the expandablestructure 956 is arranged and utilized.

In some embodiments, the device 950 may store or harness the energygenerated by the cyclical movement of the expandable structure 956 topower various components of the device 950, including the expandablestructure itself.

Electroactive polymers deflect when actuated by electrical energy. Inthe pictured embodiment, the polymeric film 964 may comprise anelectroactive polymer that acts as an insulating dielectric between thetwo electrodes 960, 962 and may deflect upon application of a voltagedifference between the two electrodes. The first electrode 960 and thesecond electrode 962 are attached to the film 964 on its first surface970 and second surface 972, respectively, to provide a voltagedifference across the active area 968. Depending upon the signals andpower received from other components of the device 950 (e.g., amicroprocessor, communication module, and/or power supply), the driver605 and/or power supply 615 appropriately energizes or deenergizes theexpandable structure 956 to restrict or allow, respectively, blood flowthrough the lumen 955 of the device 950.

When electrical energy is supplied to the electrodes 960, 962 of theexpandable structure 956, the active area 968 deflects away from thesupport body 954 into the lumen 955, thereby transitioning the flowrestrictor 952 into an active condition by narrowing the lumen 955, asshown in FIG. 15 b. Energy supplied to the electrodes 960, 962 causes achange in the electric field, thereby activating the active area 968,which deflects away from the support body 954 to assume a convex shapeextending into the lumen 955. As the film 964 deflects toward the lumen955, the thickness T of the active area 968 decreases as the unlikeelectrical charges produced by electrodes 960, 962 attract each otherand provide a compressive force between electrodes 960, 962 and anexpansion force on the film 964 in planar directions toward thecircumferential edges of the active area 968, causing the active area968 to compress between electrodes 960, 962 and stretch in the planardirections. Narrowing the lumen 955 decreases the cross-sectional areasand diameters along the length of the lumen 955 and decreases the bloodflow volume and rate through the device 950, which creates a backpressure in the area 380 proximal to the device 950 and activates thebaroreceptors in the vicinity of area 380. It is important to note thatthe expandable structure 956 is configured to expand only to the extentthat the flow restrictor 952 permits blood flow through the lumen 955even when the flow restrictor 952 is in an active condition.

In general, the active area 968 continues to deflect until mechanicalforces balance the electrostatic forces driving the deflection. Themechanical forces include, by way of non-limiting example, elasticrestoring forces of the film 964 material, the compliance of theelectrodes 960, 962, and/or any external resistance provided by a deviceand/or load coupled to the active area (e.g., biasing member 958). Thedeflection of the active area 968 as a result of the applied voltage mayalso depend on a number of other factors such as the dielectric constantof the film 964 and the dimensions of the film 964.

The electrodes 960, 962 are compliant and change shape with the film964. The configuration of the film 964 and the electrodes 960, 962provides for increasing active area 968 response with increasingdeflection away from the support body 954. In some embodiments, theexpandable structure 956 is incompressible, i.e., has a substantiallyconstant volume under stress. In these embodiments, the active area 968decreases in thickness as a result of the expansion in the planardirections. More specifically, as the active area 968 deflects into amore active condition as shown in FIG. 15 b, compression of the film 964brings the opposite charges of the electrodes 960, 962 closer togetherand the substantially simultaneous stretching of film 964 separatessimilar charges in each electrode. In one embodiment, one of theelectrodes 960, 962 functions as a ground electrode.

As shown in FIG. 15 a, when the driver 605 and/or power supply 615withdraws electrical energy from the electrodes 960, 962, the activearea 968 is returned to its original, flattened, inactive conditionagainst the support body 954. More specifically, the removal of thevoltage difference and the induced charge causes the active area 968 toflatten toward the support body 954 and the thickness T to increase. Asthe flow restrictor 952 transitions into a less active condition, theamount of intraluminal occlusion decreases to allow blood to flow at anincreased volume and rate through the lumen 955 of the device 950. Thisdecrease in intraluminal occlusion relieves the back pressure in thearea 380, thereby decreasing the activity of baroreceptor signaling inthe area 380. When the flow restrictor 952 is in an inactive condition,as shown in FIG. 15 a, blood flows through the lumen 955 of the device950 with minimal disruption in blood volume and flow rate.

Various exemplary materials suitable for use in the expandable structure956 include, by way of non-limiting example, silicone elastomers,acrylic elastomers, polyurethanes, thermoplastic elastomers, copolymerscomprising PVDF, pressure-sensitive adhesives, fluoroelastomers,polymers comprising silicone and acrylic moieties, and the like.Polymers comprising silicone and acrylic moieties may include copolymerscomprising silicone and acrylic moieties, and polymer blends comprisinga silicone elastomer and an acrylic elastomer, for example. Combinationsof some of these materials may also be used in some embodiments of thepresent disclosure.

Although the discussion has focused primarily on one type ofelectroactive polymer commonly referred to as dielectric elastomers,expandable structures 956 of the present disclosure may also incorporateother conventional electroactive polymers. As the term is used herein,an electroactive polymer refers to a polymer that responds to electricalstimulation. Other common classes of electroactive polymer suitable foruse with various embodiments of the present disclosure include, by wayof non-limiting example, electrostrictive polymers, electronicelectroactive polymers, and ionic electroactive polymers, and somecopolymers. Electrostrictive polymers are characterized by thenon-linear reaction of a electroactive polymers (relating strain to E2).Electronic electroactive polymers typically change shape or dimensionsdue to migration of electrons in response to electric field (usuallydry). Ionic electroactive polymers are polymers that change shape ordimensions due to migration of ions in response to electric field(usually wet and contains electrolyte).

In some embodiments, multiple expandable structures 956 may be utilizedto provide greater degrees of occlusion of the lumen 955 of the device950. However shaped and configured, the expandable balloon is shaped andconfigured to lack sharp angles so as to minimize the potential forthrombogenesis and/or turbulent flow within the vessel 100.

FIG. 16 provides a schematic flowchart illustrating methods ofcontrolling blood pressure using an intravascular flow-modifying deviceof the present disclosure, e.g., device 300. All of the embodiments ofintravascular flow-modifying devices disclosed herein are suitable forimplantation, and are preferably implanted using a minimally invasivepercutaneous and intravascular approach. The intravascularflow-modifying devices may be positioned anywhere within the venous orarterial vasculature where baroreceptors capable of modulating thebaroreflex system are present. The intravascular flow-modifying deviceswill generally be implanted such that the device is positioned within avessel immediately distal to a target area of the baroreceptors. For thepurposes of illustration only, the methods disclosed by FIG. 16 will bediscussed with respect to FIG. 4, which illustrates the intravascularflow-modifying device 300 positioned within the right renal vein 430.

In FIG. 16, step 1000 initiates the blood pressure control process withthe user positioning the intravascular flow-modifying device 300 withinthe right renal vein 430. Prior to insertion of the device 300, adelivery apparatus, e.g., a guidewire, may be introduced into thearterial vasculature of a patient using standard percutaneoustechniques. For example, once the guidewire is positioned within thetarget blood vessel, which is the right renal vein 430 in theillustrated embodiment of FIG. 4, the device 300 may be introduced in anunexpanded condition into the vasculature of a patient over theguidewire and advanced to the area of interest. In the alternative, thedevice 300 may be releasably coupled in an unexpanded condition to thedelivery apparatus external to the patient and both the guidewire andthe device 300 may be simultaneously introduced into the patient andadvanced to the vessel of interest.

The device 300 is implanted within the renal vasculature such that thedevice 300, which is disposed in an unexpanded condition when introducedinto the patient's vasculature, is positioned distal to the targetbaroreceptors of interest (e.g., baroreceptors 110 illustrated in FIG.3). At step 1010, the user may determine whether the device 300 isoptimally positioned within the vessel. The delivery apparatus mayinclude IVUS or other imaging apparatuses thereon, thereby permittingthe user to precisely position the device 300 within the blood vessel byusing in vivo, real-time intravascular imaging. Additionally oralternatively, the user may utilize external imaging, such as, by way ofnon-limiting example, fluoroscopy, ultrasound, CT, or MRI, to aid in theguidance and positioning of the device 300 within the patient'svasculature.

At step 1020, if the device 300 is not optimally positioned within thevessel, the user may reposition the device 300 within the vessel at step1000 and recheck the position at step 1010.

After step 1030, when the user determines that the device 300 isoptimally positioned within the vessel, the user may expand theintravascular flow-modifying device 300 within the vessel immediatelydistal to the baroreceptors of interest at step 1040. Expansion of thestent-like support body 600 of the device 300 preferably anchors thedevice against the vessel walls by applying a biasing force against thevessel walls (e.g., vessel walls 120 illustrated in FIG. 3). In theneutral, unactivated and/or unpowered condition, the flow restrictor 360of the device 300 assumes an inactive condition that does notsignificantly alter flow through the device 300.

With reference to FIGS. 5 and 16, at step 1050, the user and/or controlsystem 505 may direct any of the sensors associated with the bloodpressure control system 500 to sense and/or monitor a cardiovascularcharacteristic or parameter representative of the patient's bloodpressure and/or indicative the need to modify the activity of thebaroreflex system (e.g., baroreflex system 160 illustrated in FIG. 2).

At step 1060, the user and/or control system 505 may activate and/or useany of the remote sensors 515 of the system 500 and direct them to senseand/or monitor a cardiovascular characteristic or parameterrepresentative of the patient's blood pressure and/or indicative theneed to modify the activity of the baroreflex system 160. In someembodiments, the remote sensor 515 may comprise an external bloodpressure cuff. In other embodiments, the remote sensor 515 may comprisean internal sensor positioned within the patient's body such that it iscapable of sensing cardiovascular characteristic or parameterrepresentative of the patient's blood pressure and/or indicative theneed to modify the activity of the baroreflex system 160.

At step 1070, the sensor 515 may generate a data signal indicative ofthe sensed parameter data and send the data signal to the control system505 (in particular, to the processor 320) for processing. Additionallyor alternatively, at step 1065, the sensor 515 may send the data signalto the communication module 620 of the device 300 for internal, localprocessing by the microprocessor 610.

Additionally or alternatively, at step 1080, the user and/or controlsystem 505 may activate any of the local sensors of the system 500,including the onboard sensors 370, 372 and any auxiliary sensors 625,and direct them to sense and/or monitor a cardiovascular characteristicor parameter representative of the patient's blood pressure and/orindicative the need to modify the activity of the baroreflex system 160.In some instances, the user and/or control system 505 may only activateany of the local sensors of the system 500 if deemed necessary afterevaluating the data signal sent by the remote sensors 515.

At step 1090, the local sensors 370, 372, and/or 625 may generate a datasignal indicative of the sensed parameter data and send the data signalto the communication module 620 of the device 300.

At step 1100, the communication module 620 may send the data signal tothe on-board microprocessor 610 for local processing. Additionally oralternatively, at step 1110, the communication module 620 may send thedata signal to the control system 505 (in particular, to the processor320) for remote processing.

At step 1120, any of the remote or local processors of the system 500(e.g., the processor 320 and the microprocessor 610) and/or the userdetermines whether the sensed data indicates a need to increase thelocal blood pressure proximal to the device 300 to activate thebaroreceptors 110 proximal to the device.

If, at step 1130, the system 500 and/or the user determine that thesensed data indicates a need to increase the local blood pressureproximal to the device 300, then, at step 1140, the system 500 and/orthe user incrementally activates and/or supplies power to the flowrestrictor 360 of the device 300, thereby incrementally increasing thedegree of occlusion of the lumen 630 of the device 300 and increasingthe back pressure proximal to the device 300. For example, if the senseddata indicates a globally hypertensive situation or a locallyhypotensive situation that is unsafe for tissue health, the system 500and/or the user may activate the flow restrictor 360 at step 1140.Activating the flow restrictor 360 may induce a baroreceptor signal fromthe area proximal to the device 300 that is perceived by the brain to beexcessive blood pressure, which induces the brain to alter theactivities of the baroreflex system 160 to decrease blood pressure.

If, at step 1150, the system 500 and/or the user determine that thesensed data does not indicate a need to increase the local bloodpressure proximal to the device 300, then, at step 1160, the system 500and/or the user incrementally deactivates and/or stops or decreasespower to the flow restrictor 360 of the device 300, therebyincrementally decreasing the degree of occlusion of the lumen 630 of thedevice 300 and decreasing the back pressure proximal to the device 300.For example, if the sensed data indicates a globally hypotensive ornormotensive situation or a locally hypertensive situation that isunsafe for tissue health, the system 500 and/or the user may deactivatethe flow restrictor 360 at step 1160. Deactivating the flow restrictor360 may reduce the baroreceptor signals from the area proximal to thedevice 300. Reduced baroreceptor activity may be perceived by the brainto be normal or low blood pressure, which induces the brain to alter theactivities of the baroreflex system 160 to either maintain or increase,respectively, blood pressure.

At steps 1170 and 1180, the cycle may continue according to powerconservation algorithms determined by the system 500 and/or the desiresof the user, with the system 500 and/or the user directing any of thesensors associated with the blood pressure control system 500 to senseand/or monitor a cardiovascular characteristic or parameterrepresentative of the patient's blood pressure and/or indicative theneed to modify the activity of the baroreflex system.

Persons of ordinary skill in the art will appreciate that theembodiments encompassed by the present disclosure are not limited to theparticular exemplary embodiments described above. In that regard,although illustrative embodiments have been shown and described, a widerange of modification, change, and substitution is contemplated in theforegoing disclosure. For example, the thermal basket catheter may beutilized anywhere with a patient's vasculature, both arterial andvenous, having an indication for thermal neuromodulation. It isunderstood that such variations may be made to the foregoing withoutdeparting from the scope of the present disclosure. Accordingly, it isappropriate that the appended claims be construed broadly and in amanner consistent with the present disclosure.

We claim:
 1. A method of treating hypertension, comprising: implanting aflow restricting device in the vasculature of a patient; sensing bloodpressure; actuating the flow restricting device in response to thesensed blood pressure to modify the flow of blood through the flowrestrictor; and sensing the blood pressure after said actuating todetermine the effect of the modification of the blood flow.
 2. Themethod of claim 1, wherein the flow restricting device includes a sensorand said sensing includes activating the onboard sensor.
 3. The methodof claim 1, wherein the flow restricting device includes an electricalactuator and the step of actuating includes sending an electrical signalto the actuator.
 4. The method of claim 2, wherein the flow restrictingdevice includes a power supply, and the sensing step includes poweringthe sensor.
 5. The method of claim 1, wherein the flow restrictingdevice includes a power harvesting mechanism, the method furtherincluding harvesting power from the body and using the power for atleast one of actuating or sensing.
 6. A vascular flow regulation device,comprising: an anchoring body configured for fixed engagement with anvascular wall; a flow constriction element coupled to the anchoringbody, the flow constriction element movable between a high flow positionand a low flow position; and an actuator coupled to the flowconstriction element, the actuator configured to move the flowconstriction element between the high flow position and the low flowposition.
 7. The device of claim 6, wherein the actuator is aelectrically powered.
 8. The device of claim 7, further including apower supply carried by the anchoring body.
 9. A vascular flowregulation device, comprising: an anchoring body configured for fixedengagement with an vascular wall; a flow constriction element coupled tothe anchoring body, the flow constriction element movable between a highflow position and a low flow position; and a sensing element coupled tothe anchoring body and configured to detect at least one biometricparameter.
 10. The device of claim 9, wherein the sensing elementgenerates a signal and further including an actuator joined to the flowconstricting device for moving the flow constricting element between thehigh flow and low flow positions in response to the signal.
 11. Thedevice of claim 9, wherein the sensing element sense blood pressure. 12.The device of claim 6, wherein the actuator is configured to return tothe high flow condition in the absence of power.